Glycolic Acid → 6-bromo-4-(((3aS,4R,5R,6aS)-2-(2-hydroxyacetyl)-4-methyloctahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877737ノート

反応式

HRID 877737 の反応式
C(N(CC)C(C)C)(C)C.OC(C(F)(F)F)=O.[Br:17][C:18]1[CH:19]=[C:20]2[C:25]([NH:26][C@@H:27]3[CH2:34][C@@H:30]4[CH2:31][NH:32][CH2:33][C@@H:29]4[C@H:28]3[CH3:35])=[C:24]([C:36]([NH2:38])=[O:37])[CH:23]=[N:22][N:21]2[CH:39]=1.[OH:40][CH2:41][C:42](O)=[O:43]>CN(C)C=O.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>[Br:17][C:18]1[CH:19]=[C:20]2[C:25]([NH:26][C@@H:27]3[CH2:34][C@@H:30]4[CH2:31][N:32]([C:41](=[O:40])[CH2:42][OH:43])[CH2:33][C@@H:29]4[C@H:28]3[CH3:35])=[C:24]([C:36]([NH2:38])=[O:37])[CH:23]=[N:22][N:21]2[CH:39]=1

参加物

7

反応物 3

HCID 757Glycolic AcidHCID 81531DiisopropylethylamineHCID 867078986-bromo-4-(((3aS,4R,5R,6aS)-4-methyloctahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide TFA salt

生成物 1

HCID 682908906-bromo-4-(((3aS,4R,5R,6aS)-2-(2-hydroxyacetyl)-4-methyloctahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide収率 94.7%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

N,N-diisopropylethylamine (0.532 mL, 3.05 mmol) was added to a solution of 6-bromo-4-(((3 aS,4R,5R,6aS)-4-methyloctahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide TFA salt from Step 2 of Example 59 (250 mg, 0.508 mmol), 2-hydroxyacetic acid (77 mg, 1.016 mmol) and (benzotriazol-1-yloxy)tris(dimethylamine)phosphonium hexafluorophosphate (449 mg, 1.016 mmol) in N,N-dimethylformamide (5 mL). After 1 h at room temperature, the mixture was diluted with saturated sodium bicarbonate (5 mL) and ethyl acetate (100 mL), washed with water, brine, dried (MgSO4) and concentrated to give the expected product (210 mg). This material was used in the next reaction without purification. 1H NMR (400 MHz, methanol-d4) δ ppm 8.13 (1 H, s), 7.63 (1 H, s), 7.03 (1 H, d, J=1.32 Hz), 4.83-4.96 (2 H, m), 4.06-4.36 (2 H, m), 3.43-3.75 (3 H, m), 3.04-3.10 (1 H, m), 2.80-2.85 (1 H, m), 2.41-2.58 (1 H, m), 1.60-1.94 (1 H, m), 1.39-1.56 (1 H, m), 1.08-1.20 (3 H, m), MS (ES+) m/z: 436.1, 438.2 (M+H).

後処理

  1. washwashed with water, brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated

出典と根拠

ORDレコード
ord-8547f0d29d894f77bc79b027b0117222
出典データセット
uspto-grants-2015_03
特許番号
US08987268B2

反応ノート

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