Cesium carbonate → HCID 67230028, 화합물

HRID 1844323노트

반응식

HRID 1844323 반응식
Cl.Cl.[C@H:3]12[CH2:9][C@H:6]([NH:7][CH2:8]1)[CH2:5][N:4]2[C:10]([C@@:12]1([C:26]2([OH:30])[CH2:29][CH2:28][CH2:27]2)[CH2:16][CH2:15][C@@H:14]([NH:17][C@@H:18]2[C@H:23]([O:24][CH3:25])[CH2:22][O:21][CH2:20][CH2:19]2)[CH2:13]1)=[O:11].I[C:32]1[CH:37]=[N:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[N:33]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.CS(C)=O.[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[NH3:4].[OH:30][C:26]1([C@:12]2([C:10]([N:4]3[CH2:5][C@@H:6]4[CH2:9][C@H:3]3[CH2:8][N:7]4[C:32]3[CH:37]=[N:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[N:33]=3)=[O:11])[CH2:16][CH2:15][C@@H:14]([NH:17][C@@H:18]3[C@H:23]([O:24][CH3:25])[CH2:22][O:21][CH2:20][CH2:19]3)[CH2:13]2)[CH2:29][CH2:28][CH2:27]1

참가 물질

9

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 200966762-Iodo-6-(trifluoromethyl)pyrazineHCID 67228799HCID 67228799, 화합물

생성물 2

HCID 222Ammonia수율 2%HCID 67230028HCID 67230028, 화합물수율 82%

시약·촉매·용매 3

HCID 44556509Tris(dibenzylideneacetone) palladium촉매HCID 679Dimethyl Sulfoxide용매HCID 312751,4-Dioxane용매

실험 절차

A solution of 93 mg (0.20 mmol) of 1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-ylcarbonyl]-3-(1-hydroxycyclobutyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol dihydrochloride 121 mg (0.442 mmol) of 2-iodo-6-trifluoromethylpyrazine, 326 mg (1.0 mmol) of cesium carbonate, 24 mg (40 umol) of XantPhos, and 16 mg (28 umol) of tris(dibenzylideneacetone) palladium (0) in 0.8 mL of dioxane and 0.4 mL of DMSO was heated at 80 C under argon for 18 h, then cooled and partitioned between ethyl acetate and water. The organic phase was dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography of the residue on silica using 0-2-4% methanolic ammonia and 3% methanol in dichloromethane afforded 89 mg (82%) of the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.51-2.40 (m, 16H) 2.65-2.74 (m, 1H) 3.09-3.49 (m, 10H) 3.54 (d, J=9.6 Hz, 1H) 3.61-3.80 (m, 2H) 3.88-3.96 (m, 1H) 4.06 (dd, J=12.5, 2.9 Hz, 1H) 4.96 (br. s., 1H) 5.21 (br. s., 1H) 8.02 (s, 1H) 8.15 (s, 1H). HRMS calculated for C26H36N5O4F3: 540.2797. found: 540.2896.

후처리

  1. temperaturecooled
  2. custompartitioned between ethyl acetate and water
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-fb1be6b9523f4245909755fcb87917f3
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946413B2

반응 노트

불러오는 중…