Triethylamine → tert-Butyl [(1R,3S)-3-[(3R)-Tetrahydrofuran-3-yl]-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]carbamate

HRID 1044633노트

반응식

HRID 1044633 반응식
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][CH2:12][C@:11]([C@H:17]2[CH2:21][CH2:20][O:19][CH2:18]2)([C:14]([OH:16])=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[F:24][C:25]([F:39])([F:38])[C:26]1[CH:31]=[CH:30][N:29]=[C:28]([N:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[CH:27]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C=O)C.C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]1[CH2:13][CH2:12][C@:11]([C@H:17]2[CH2:21][CH2:20][O:19][CH2:18]2)([C:14]([N:35]2[CH2:36][CH2:37][N:32]([C:28]3[CH:27]=[C:26]([C:25]([F:39])([F:24])[F:38])[CH:31]=[CH:30][N:29]=3)[CH2:33][CH2:34]2)=[O:16])[CH2:10]1)([CH3:2])([CH3:3])[CH3:4]

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68596411(1S,3R)-3-[(tert-Butoxycarbonyl)amino]-1-[(3R)-tetrahydrofuran-3-yl]cyclopentanecarboxylic AcidHCID 685975881-[4-(Trifluoromethyl)pyridin-2-yl]piperazine dihydrochloride

생성물 1

HCID 86641538tert-Butyl [(1R,3S)-3-[(3R)-Tetrahydrofuran-3-yl]-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]carbamate수율 45.1%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

(1S,3R)-3-[(tert-Butoxycarbonyl)amino]-1-[(3R)-tetrahydrofuran-3-yl]cyclopentanecarboxylic acid (350.0 mg, 1.169 mmol), 1-[4-(trifluoromethyl)pyridin-2-yl]piperazine dihydrochloride (391.1 mg, 1.286 mmol), triethylamine (0.652 mL, 4.68 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (665.1 mg, 1.754 mol) (HBTU) were mixed in dry DMF (8.0 mL). After being stirred at room temperature overnight, the reaction mixture was diluted with CH2Cl2 and washed with saturated Na2CO3. The aqueous layer was extracted with CH2Cl2 four times. The combined organic layers were dried (MgSO4), concentrated and purified by flash chromatography (Combi-flash system, 0-50% EtOAc in hexanes, gradient elution, 40 gram column) to provide the desired product (270 mg, 45%). MS calculated for C25H36F3N4O4 (M+H) 513.3; found 513.3.

후처리

  1. washwashed with saturated Na2CO3
  2. extractionThe aqueous layer was extracted with CH2Cl2 four times
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated
  5. custompurified by flash chromatography (Combi-flash system, 0-50% EtOAc in hexanes, gradient elution, 40 gram column)

출처 및 근거

ORD 기록
ord-204bf24ea6f943b5b4fd533ebce424bf
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08563582B2

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