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 877739Notes

Reaction equation

HRID 877739 reaction equation
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

Participants

6

Reactant 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

Product 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-carboxamideYield 84.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-15399709a9ea4515827aedfc01f698ec
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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