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 877737Notes

Reaction equation

HRID 877737 reaction equation
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

Participants

7

Reactant 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

Product 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-carboxamideYield 94.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

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).

Workup

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

Sources & evidence

ORD record
ord-8547f0d29d894f77bc79b027b0117222
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

Loading…