Sodium Carbonate → tert-butyl (S)-2-(4-chlorophenyl)-3-(4-((R)-7,7-difluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]-pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

HRID 82394노트

반응식

HRID 82394 반응식
Cl.Cl.[F:3][C:4]1([F:20])[C:8]2[N:9]=[CH:10][N:11]=[C:12]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[C:7]=2[C@H:6]([CH3:19])[CH2:5]1.[C:21]([O:25][C:26]([N:28]([CH:41]([CH3:43])[CH3:42])[CH2:29][C@H:30]([C:34]1[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=1)[C:31](O)=[O:32])=[O:27])([CH3:24])([CH3:23])[CH3:22].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.CC(=O)OCC>[Cl:40][C:37]1[CH:38]=[CH:39][C:34]([C@H:30]([C:31]([N:16]2[CH2:17][CH2:18][N:13]([C:12]3[C:7]4[C@H:6]([CH3:19])[CH2:5][C:4]([F:3])([F:20])[C:8]=4[N:9]=[CH:10][N:11]=3)[CH2:14][CH2:15]2)=[O:32])[CH2:29][N:28]([CH:41]([CH3:42])[CH3:43])[C:26](=[O:27])[O:25][C:21]([CH3:23])([CH3:22])[CH3:24])=[CH:35][CH:36]=1

참가 물질

8

반응물 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59564929(2S)-3-[tert-butoxycarbonyl(isopropyl)amino]-2-(4-chlorophenyl)propanoic acidHCID 66846210(R)-7,7-difluoro-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochloride

생성물 1

HCID 67338612tert-butyl (S)-2-(4-chlorophenyl)-3-(4-((R)-7,7-difluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]-pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate수율 68%

시약·촉매·용매 2

HCID 6344Dichloromethane용매2회HCID 8857Ethyl Acetate용매2회

실험 절차

To a solution of (R)-7,7-difluoro-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochloride (0.015 g, 0.046 mmol), (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.016 g, 0.046 mmol), and DIEA (0.024 ml, 0.14 mmol) in 1.7 mL DCM was added HBTU (0.017 g, 0.046 mmol). The reaction mixture was stirred 15 hours, after which 2M Na2CO3 was added. The mixture was extracted with DCM, and the combined extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified on silica gel (Biotage 12S) by first flushing with about 120 mL 5:1 DCM:EA, then gradient to 1:1 DCM:EA to give tert-butyl(S)-2-(4-chlorophenyl)-3-(4-((R)-7,7-difluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]-pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (0.018 g, 68% yield) as a white foam. MS (APCI)+ m/z 578 [M+H]+.

후처리

  1. extractionThe mixture was extracted with DCM
  2. dry with materialthe combined extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude was purified on silica gel (Biotage 12S)
  6. customby first flushing with about 120 mL 5:1 DCM

출처 및 근거

ORD 기록
ord-18e929e74b754b77b92396335656add8
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846681B2

반응 노트

불러오는 중…