Diisopropylethylamine → 6-bromo-4-(((3R,4S)-1-(1-cyanocyclopropanecarbonyl)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877822Notes

Reaction equation

HRID 877822 reaction equation
I.[Br:2][C:3]1[CH:4]=[C:5]2[C:10]([NH:11][C@H:12]3[C@@H:16]([O:17][CH3:18])[CH2:15][NH:14][CH2:13]3)=[C:9]([C:19]([NH2:21])=[O:20])[CH:8]=[N:7][N:6]2[CH:22]=1.[C:23]([C:25]1([C:28](O)=[O:29])[CH2:27][CH2:26]1)#[N:24].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[Br:2][C:3]1[CH:4]=[C:5]2[C:10]([NH:11][C@H:12]3[C@@H:16]([O:17][CH3:18])[CH2:15][N:14]([C:28]([C:25]4([C:23]#[N:24])[CH2:27][CH2:26]4)=[O:29])[CH2:13]3)=[C:9]([C:19]([NH2:21])=[O:20])[CH:8]=[N:7][N:6]2[CH:22]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27332591-Cyanocyclopropanecarboxylic acidHCID 682919346-bromo-4-(((3R,4S)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide

Product 1

HCID 682909856-bromo-4-(((3R,4S)-1-(1-cyanocyclopropanecarbonyl)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamideYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 6-bromo-4-(((3R,4S)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide (260 mg, 0.54 mmol) in DMF (1 mL) at rt, was added 1-cyanocyclopropanecarboxylic acid (66 mg, 0.6 mmol), BOP (287 mg, 0.65 mmol) and DIPEA (0.3 mL, 1.7 mmol). The mixture was stirred for 2 h. The reaction was added water, stirred at rt for 2 h, filtered and rinsed with water to give 6-bromo-4-(((3R,4S)-1-(1-cyanocyclopropanecarbonyl)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (192 mg, 80% yield) as a brown solid. 1H NMR (400 MHz, METHANOL-d4) δ 8.17 (d, J=6.6 Hz, 1H), 7.68 (d, J=7.0 Hz, 1H), 7.11 (d, J=17.8 Hz, 1H), 5.09-4.92 (m, 2H), 4.55 (br. s., 2H), 4.46-3.93 (m, 3H), 3.88-3.59 (m, 2H), 3.50 (d, J=14.1 Hz, 3H), 1.75-1.46 (m, 4H); MS (ES+) m/z: 446.1, 447.2 (M+H); LC retention time: 3.49 min (analytical HPLC Method B).

Workup

  1. stirringstirred at rt for 2 h
  2. filtrationfiltered
  3. washrinsed with water

Sources & evidence

ORD record
ord-a4b2313a10b049feaceb6b938cd62e22
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

Loading…