Diisopropylethylamine → (3S,4S)-benzyl 3-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-(fluoromethyl)pyrrolidine-1-carboxylate

HRID 877798Notes

Reaction equation

HRID 877798 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](Cl)=[C:8]([C:11]([NH2:13])=[O:12])[CH:7]=[N:6][N:5]2[CH:14]=1.[NH2:15][C@H:16]1[C@@H:20]([CH2:21][F:22])[CH2:19][N:18]([C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])[CH2:17]1.CCN(C(C)C)C(C)C>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:15][C@H:16]3[C@@H:20]([CH2:21][F:22])[CH2:19][N:18]([C:23]([O:25][CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[O:24])[CH2:17]3)=[C:8]([C:11](=[O:12])[NH2:13])[CH:7]=[N:6][N:5]2[CH:14]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 682911926-Bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide2×HCID 68350298(3S,4S)-benzyl 3-amino-4-(fluoromethyl)pyrrolidine-1-carboxylate2×

Product 1

HCID 86707902(3S,4S)-benzyl 3-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-(fluoromethyl)pyrrolidine-1-carboxylateYield 80.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 2, 740 mg, 2.70 mmol), (3S,4S)-benzyl 3-amino-4-(fluoromethyl)pyrrolidine-1-carboxylate (Intermediate 10, 714 mg, 2.83 mmol) and DIPEA (0.989 mL, 5.66 mmol) in DMF (8 mL) was heated to 80° C. for 16 hrs. The reaction mixture was concentrated and purified on silica gel column with Hexanes/EtOAc (1/1) to give the title compound (1.06 g, 80% yield). 1H NMR (500 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.94 (br. s., 1H), 7.42-7.27 (m, 5H), 7.15 (s, 1H), 5.16-4.94 (m, 3H), 4.70-4.54 (m, 2H), 3.90-3.41 (m, 4H), 3.02-2.84 (m, 1H), MS (ES+) m/z: 490.1, 492.1 (M+H); LC retention time: 3.261 min (analytical HPLC Method H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified on silica gel column with Hexanes/EtOAc (1/1)

Sources & evidence

ORD record
ord-fa4b1f5fba214ac1850ecc51dea3fb9a
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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