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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 5-chloro-4-(9'-cyclohexyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepine]-2'-ylamino)-N-(4-dimethylaminocyclohexyl)-2-fluoro-benzamide

HRID 2234340
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HRID 2234340 반응식
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[C:8]3([CH2:20][CH2:19]3)[CH2:9][N:10]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[C:11]=2[N:12]=1.[NH2:23][C:24]1[C:41]([Cl:42])=[CH:40][C:27]([C:28]([NH:30][CH:31]2[CH2:36][CH2:35][CH:34]([N:37]([CH3:39])[CH3:38])[CH2:33][CH2:32]2)=[O:29])=[C:26]([F:43])[CH:25]=1.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.[Pd+2].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>[Cl:42][C:41]1[C:24]([NH:23][C:2]2[N:3]=[CH:4][C:5]3[N:6]([CH3:22])[C:7](=[O:21])[C:8]4([CH2:19][CH2:20]4)[CH2:9][N:10]([CH:13]4[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]4)[C:11]=3[N:12]=2)=[CH:25][C:26]([F:43])=[C:27]([CH:40]=1)[C:28]([NH:30][CH:31]1[CH2:32][CH2:33][CH:34]([N:37]([CH3:39])[CH3:38])[CH2:35][CH2:36]1)=[O:29]
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반응물 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 579698842'-chloro-9'-cyclohexyl-5'-methyl-8',9'-dihydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepin]-6'(5'H)-one2회HCID 686828744-amino-5-chloro-N-(4-dimethylaminocyclohexyl)-2-fluoro-benzamide2회

생성물 1

HCID 68682573
5-chloro-4-(9'-cyclohexyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepine]-2'-ylamino)-N-(4-dimethylaminocyclohexyl)-2-fluoro-benzamide
수율 28.2%

시약·촉매·용매 2

HCID 9897284tris(dibenzylideneacetone) palladium (II)촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

2′-chloro-9′-cyclohexyl-5′-methyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 270; 103 mg, 0.32 mmol), 4-amino-5-chloro-N-(4-dimethylaminocyclohexyl)-2-fluoro-benzamide (Intermediate 175; 92 mg, 0.29 mmol), and XANTPHOS (16 mg, 0.03 mmol) were dissolved in 1,4-dioxane (7.5 mL). Caesium 10 carbonate (210 mg, 0.59 mmol) was added and the system purged with a stream of nitrogen for 15 minutes before tris(dibenzylideneacetone) palladium (II) (17 mg, 0.02 mmol) was added. The apparatus was evacuated and backfilled with nitrogen (×3) and then heated at 100° C. for 3 hours. The mixture was cooled, filtered and the filtrate absorbed on to an SCX column, and the column then washed with methanol and eluted with ammonia in methanol. Product containing fractions were combined and evaporated and the residue purified by base modified reverse phase preparative HPLC to yield the title compound as a white solid (49 mg, 28%).

후처리

  1. additionwas added
  2. customThe apparatus was evacuated
  3. temperatureThe mixture was cooled
  4. filtrationfiltered
  5. customthe filtrate absorbed on to an SCX column
  6. washthe column then washed with methanol
  7. washeluted with ammonia in methanol
  8. additionProduct containing fractions
  9. customevaporated
  10. customthe residue purified by base modified reverse phase preparative HPLC

출처 및 근거

ORD 기록
ord-3855e6edb4d44478aa36662672d8eb8f
출처 데이터셋
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07709471B2

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