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 1052131ノート

反応式

HRID 1052131 の反応式
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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane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 trifluoroacetate (3.9 g, 9.77 mmol), (3-carbamoyl-indazol-1-yl)-acetic acid (prepared as described in Part A, 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 under a nitrogen atmosphere. 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) to afford the title compound. Rf, TLC (EtOAc)=0.85; MS (UPLC): 436.3 [M+NH4]+, 463.2 [M+HCOO]−; tR (HPLC conditions b): 1.82 min.

後処理

  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)

出典と根拠

ORDレコード
ord-06b8cf95b7dd45bf91b3793eaa6d656c
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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