Diisopropylethylamine → (1R,3S,5R)-2-[2-(3-Carbamoyl-indazol-1-yl)-acetyl]-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester

HRID 1527439노트

반응식

HRID 1527439 반응식
FC(F)(F)C(O)=O.[CH2:8]([O:15][C:16]([C@@H:18]1[CH2:23][C@@H:22]2[C@@H:20]([CH2:21]2)[NH:19]1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:24]([C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[N:29]([CH2:36][C:37](O)=[O:38])[N:28]=1)(=[O:26])[NH2:25].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.O>[CH2:8]([O:15][C:16]([C@@H:18]1[CH2:23][C@@H:22]2[C@@H:20]([CH2:21]2)[N:19]1[C:37](=[O:38])[CH2:36][N:29]1[C:30]2[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:27]([C:24](=[O:26])[NH2:25])=[N:28]1)=[O:17])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682833421386457-64-2HCID 68284347(1R,3S,5R)-2-Aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester trifluoroacetate

생성물 1

HCID 68283506(1R,3S,5R)-2-[2-(3-Carbamoyl-indazol-1-yl)-acetyl]-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

To a solution of (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester trifluoroacetate (3.9 g, 9.77 mmol), (3-carbamoyl-indazol-1-yl)-acetic acid (prepared as described in Scheme A25, 2.26 g, 9.77 mmol), HBTU (5.56 g, 14.66 mmol) in CH2Cl2 (60 mL) was added DIPEA (5.12 mL, 29.3 mmol). The reaction mixture was stirred for 48 h at RT. The reaction mixture was poured into water and extracted with CH2Cl2 (×3). The combined organic extracts were dried over Na2SO4, filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 10:0 to 0:10). Rf, TLC (EtOAc)=0.85; MS (UPLC): 436.3 [M+NH4]+, 463.2 [M+HCOO]−; tR (HPLC conditions f): 1.82 min.

후처리

  1. extractionextracted with CH2Cl2 (×3)
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 10:0 to 0:10)
  6. custom1.82 min.

출처 및 근거

ORD 기록
ord-cf407b677eec498ab02bb2d934368ff1
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085555B2

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