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

HRID 877739ノート

反応式

HRID 877739 の反応式
OC(C(F)(F)F)=O.[Br:8][C:9]1[CH:10]=[C:11]2[C:16]([NH:17][C@@H:18]3[CH2:25][C@@H:21]4[CH2:22][NH:23][CH2:24][C@@H:20]4[C@H:19]3[CH3:26])=[C:15]([C:27]([NH2:29])=[O:28])[CH:14]=[N:13][N:12]2[CH:30]=1.[OH:31][C:32]([CH3:37])([CH3:36])[C:33](O)=[O:34].C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[Br:8][C:9]1[CH:10]=[C:11]2[C:16]([NH:17][C@@H:18]3[CH2:25][C@@H:21]4[CH2:22][N:23]([C:33](=[O:34])[C:32]([OH:31])([CH3:37])[CH3:36])[CH2:24][C@@H:20]4[C@H:19]3[CH3:26])=[C:15]([C:27]([NH2:29])=[O:28])[CH:14]=[N:13][N:12]2[CH:30]=1

参加物

6

反応物 3

HCID 8471TriethylamineHCID 116712-Hydroxyisobutyric acidHCID 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 682908626-bromo-4-(((3aS,4R,5R,6aS)-2-(2-hydroxy-2-methylpropanoyl)-4-methyloctahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide収率 84.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of 6-bromo-4-(((3aS,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 (151 mg, 0.307 mmol), 2-hydroxy-2-methylpropanoic acid (38.3 mg, 0.368 mmol), triethylamine (0.128 mL, 0.920 mmol) and (benzotriazol-1-yloxy)tris(dimethylamine)phosphonium hexafluorophosphate (163 mg, 0.368 mmol) in dimethylformamide (2 mL) was stirred at room temperature for 2 h. The mixture was diluted with ethyl acetate (80 mL), washed with saturated sodium bicarbonate, water, brine, dried (MgSO4) and concentrated to give the expected product (120 mg). 1H NMR (400 MHz, methanol-d4) d 8.13 (s, 1H), 7.63 (d, J=1.8 Hz, 1H), 7.03 (d, J=1.8 Hz, 1H), 4.35-4.03 (m, 2H), 3.99-3.51 (m, 3H), 2.88-2.79 (m, 1H), 2.72-2.66 (m, 2H), 1.82-1.61 (m, 2H), 1.47-1.39 (m, 6H), 1.16 (d, J=6.6 Hz, 3H); MS (ES+) m/z: 436.1, 438.2 (M+H); LCMS (M+1): 464.1, 466.2.

後処理

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

出典と根拠

ORDレコード
ord-15399709a9ea4515827aedfc01f698ec
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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