Dichloromethane → (5R,7R)-4-(4-((S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoyl)-1,4-diazepan-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate

HRID 2192451노트

반응식

HRID 2192451 반응식
Cl.[N+:2]([C:5]1[CH:30]=[CH:29][C:8]([C:9]([O:11][C@H:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([N:21]4[CH2:27][CH2:26][CH2:25][NH:24][CH2:23][CH2:22]4)[C:15]=3[C@H:14]([CH3:28])[CH2:13]2)=[O:10])=[CH:7][CH:6]=1)([O-:4])=[O:3].[C:31]([O:35][C:36]([N:38]([CH:51]([CH3:53])[CH3:52])[CH2:39][CH:40]([C:44]1[CH:49]=[CH:48][C:47]([Cl:50])=[CH:46][CH:45]=1)[C:41](O)=[O:42])=[O:37])([CH3:34])([CH3:33])[CH3:32].ClCCl.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>>[N+:2]([C:5]1[CH:6]=[CH:7][C:8]([C:9]([O:11][C@H:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([N:21]4[CH2:27][CH2:26][CH2:25][N:24]([C:41](=[O:42])[C@@H:40]([C:44]5[CH:45]=[CH:46][C:47]([Cl:50])=[CH:48][CH:49]=5)[CH2:39][N:38]([C:36]([O:35][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:37])[CH:51]([CH3:52])[CH3:53])[CH2:23][CH2:22]4)[C:15]=3[C@H:14]([CH3:28])[CH2:13]2)=[O:10])=[CH:29][CH:30]=1)([O-:4])=[O:3]

참가 물질

5

반응물 4

HCID 6344DichloromethaneHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 251786973-{[(tert-Butoxy)carbonyl](propan-2-yl)amino}-2-(4-chlorophenyl)propanoic acidHCID 67436383(5R,7R)-4-(1,4-Diazepan-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate hydrochloride

생성물 1

HCID 67437824(5R,7R)-4-(4-((S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoyl)-1,4-diazepan-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate수율 50%

실험 절차

(5R,7R)-4-(1,4-Diazepan-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate hydrochloride (61 mg, 0.140 mmol) and 3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (48 mg, 0.140 mmol) were suspended in dichloromethane (5 mL) N,N-Diisopropylethylamine (54 mg, 0.420 mmol) was then added. HBTU (53 mg, 0.140 mmol) was added, and the resultant solution was stirred at ambient for 16 hours. After this time, the reaction mixture was quenched by the addition of saturated sodium carbonate solution and then extracted twice with dichloromethane. The combined organic portions were dried over sodium sulfate, filtered, and concentrated. The residue thus obtained was purified by silica gel chromatography to give (5R,7R)-4-(4-((S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoyl)-1,4-diazepan-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (50 mg, 50%). LCMS (APCI+) M+=721.1, Rt=4.51 min.

후처리

  1. additionwas then added
  2. customAfter this time, the reaction mixture was quenched by the addition of saturated sodium carbonate solution
  3. extractionextracted twice with dichloromethane
  4. dry with materialThe combined organic portions were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue thus obtained
  8. customwas purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-1f1e9cab5d0c406dae479ab719b2fcc2
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08329709B2

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