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 877737노트

반응식

HRID 877737 반응식
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

참가 물질

7

반응물 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

생성물 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-carboxamide수율 94.7%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매HCID 516892Sodium Bicarbonate용매

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-8547f0d29d894f77bc79b027b0117222
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987268B2

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