Diisopropylethylamine → (1R,3S,5R)-2-[2-(3-Acetyl-pyrazolo[3,4-c]pyridin-1-yl)-acetyl]-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester

HRID 1052127노트

반응식

HRID 1052127 반응식
Cl.[CH2:2]([O:9][C:10]([C@@H:12]1[CH2:17][C@@H:16]2[C@@H:14]([CH2:15]2)[NH:13]1)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:18]([C:21]1[C:29]2[C:24](=[CH:25][N:26]=[CH:27][CH:28]=2)[N:23]([CH2:30][C:31](O)=[O:32])[N:22]=1)(=[O:20])[CH3:19].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>CN(C=O)C>[CH2:2]([O:9][C:10]([C@@H:12]1[CH2:17][C@@H:16]2[C@@H:14]([CH2:15]2)[N:13]1[C:31](=[O:32])[CH2:30][N:23]1[C:24]2=[CH:25][N:26]=[CH:27][CH:28]=[C:29]2[C:21]([C:18](=[O:20])[CH3:19])=[N:22]1)=[O:11])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682838632-(3-Acetylpyrazolo[5,4-c]pyridin-1-yl)acetic acidHCID 90020119(1R,3S,5R)-2-Aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester hydrochloride

생성물 1

HCID 90019996(1R,3S,5R)-2-[2-(3-Acetyl-pyrazolo[3,4-c]pyridin-1-yl)-acetyl]-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester hydrochloride (2.98 g, 9.06 mmol), (3-acetyl-pyrazolo[3,4-c]pyridin-1-yl)-acetic acid (prepared as described in Part A, 3.2 g, 9.06 mmol) and HBTU (5.15 g, 13.59 mmol) in DMF (30.2 mL) was added DIPEA (4.75 mL, 27.2 mmol). The reaction mixture was stirred for 16 h at RT under a nitrogen atmosphere. DMF was evaporated. The residue was diluted in EtOAc and washed with aq. HCl 1N then with NaHCO3 (5% in water). The organic layer was dried (Phase separator) and concentrated. The residual oil was purified by flash column chromatography on silica gel (c-hexane/EtOAc 10:0 to 0:10) to give the title compound. TLC, Rf (EtOAc)=0.33; MS (UPLC-MS): 419 [M+H]+; tR (HPLC conditions d): 2.97 min.

후처리

  1. customDMF was evaporated
  2. additionThe residue was diluted in EtOAc
  3. washwashed with aq. HCl 1N
  4. customThe organic layer was dried (Phase separator)
  5. concentrationconcentrated
  6. customThe residual oil was purified by flash column chromatography on silica gel (c-hexane/EtOAc 10:0 to 0:10)

출처 및 근거

ORD 기록
ord-248f956998c5435fb01edd4ffe1bbe3a
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09388199B2

반응 노트

불러오는 중…