홈MCP워크벤치Skills
홈워크벤치알림마이페이지
llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
  1. 홈
  2. /반응

Cesium carbonate → (R)-10-(3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-yn-1-yl)-3-((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

HRID 575268
노트
인쇄 미리보기

반응식

HRID 575268 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[C:12]([CH2:16]Cl)=[C:13](I)[N:14]=[C:7]3[C:6]=2[CH:18]=1.[CH3:19][C:20]1[NH:24][C:23]2[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=2[N:21]=1.[C:29]([O-:32])([O-])=O.[Cs+].[Cs+].BrC1C=CC2OCC[N:42]3C(CN4C5C=CC=CC=5N=C4C)=C(I)N=C3C=2C=1.C[Si](N[Si](C)(C)C)(C)C.[CH3:71][C:72]1[O:76][N:75]=[C:74]([C@:77]([OH:81])([C:79]#[CH:80])[CH3:78])[CH:73]=1>CN(C)C=O.O.CS(C)=O.BrC1C=CC2OCCN3C(CN4C5C=CC=CC=5N=C4C)=C(C(N)=O)N=C3C=2C=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:81][C@:77]([C:74]1[CH:73]=[C:72]([CH3:71])[O:76][N:75]=1)([CH3:78])[C:79]#[C:80][C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[C:12]([CH2:16][N:21]4[C:22]5[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=5[N:24]=[C:20]4[CH3:19])=[C:13]([C:29]([NH2:42])=[O:32])[N:14]=[C:7]3[C:6]=2[CH:18]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

13

반응물 6

HCID 10796Cesium carbonateHCID 119842-MethylbenzimidazoleHCID 13838HexamethyldisilazaneHCID 58221468(R)-2-(5-methylisoxazol-3-yl)but-3-yn-2-olHCID 8669329310-Bromo-3-(chloromethyl)-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineHCID 8669329410-bromo-2-iodo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

생성물 1

HCID 86693292(R)-10-(3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-yn-1-yl)-3-((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide수율 31%

시약·촉매·용매 6

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 679Dimethyl Sulfoxide용매HCID 962Water용매2회HCID 6228Dimethylformamide용매2회HCID 8669328810-bromo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide용매

실험 절차

A mixture of 10-bromo-3-(chloromethyl)-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (200 mg, 0.46 mmol, 1.00 equiv), 2-methyl-1H-1,3-benzodiazole (304 mg, 2.30 mmol, 5.00 equiv), Cs2CO3 (450 mg, 1.38 mmol, 3.00 equiv) in N,N-dimethylformamide (2 mL) was stirred overnight at room temperature. The reaction mixture was diluted with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (10:1). This resulted in 140 mg (57%) of 10-bromo-2-iodo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine as a colorless solid. Similar to Example 10 (carbonylative amidation) a 20-mL sealed tube purged and maintained with an inert atmosphere of CO(g), was placed a solution of 10-bromo-2-iodo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (140 mg, 0.26 mmol, 1.00 equiv), HMDS (105 mg, 0.65 mmol, 2.50 equiv), Pd(dppf)Cl2 (21 mg, 0.10 equiv), and N,N-dimethylformamide (2 mL). The resulting solution was heated to 70° C. for 4 h and diluted with water. Then the resulting solution was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (10:1). This resulted in 90 mg (76%) of 10-bromo-3-((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide as a yellow solid. Similar to as described in General Procedure E with the exceptions of using Pd(PPh3)4 in DMSO, 10-bromo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide was reacted with (R)-2-(5-methylisoxazol-3-yl)but-3-yn-2-ol to give the titled compound as a yellow solid (29 mg, 31%).

후처리

  1. extractionextracted with ethyl acetate
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customThis resulted in 140 mg (57%) of 10-bromo-2-iodo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine as a colorless solid
  5. customSimilar to Example 10 (carbonylative amidation) a 20-mL sealed tube
  6. custompurged
  7. temperaturemaintained with an inert atmosphere of CO(g)
  8. temperatureThe resulting solution was heated to 70° C. for 4 h
  9. extractionThen the resulting solution was extracted with ethyl acetate
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated under vacuum
  12. customThis resulted in 90 mg (76%) of 10-bromo-3-((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide as a yellow solid

출처 및 근거

ORD 기록
ord-67a671aa80da4c0496788da7072b1988
출처 데이터셋
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09034866B2

반응 노트

불러오는 중…

이 페이지에서참가 물질실험 절차후처리출처 및 근거반응 노트