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 1052127ノート

反応式

HRID 1052127 の反応式
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

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-248f956998c5435fb01edd4ffe1bbe3a
出典データセット
uspto-grants-2016_07
特許番号
US09388199B2

反応ノート

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