Nitrogen → ethyl 2-(4-(3-carbamoyl-4-(((3S,4S)-1-(5-cyanopyridin-2-yl)-4-methylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazin-6-yl)-1H-pyrazol-1-yl)acetate

HRID 877768Notes

Reaction equation

HRID 877768 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@H:11]3[C@@H:15]([CH3:16])[CH2:14][N:13]([C:17]4[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][N:18]=4)[CH2:12]3)=[C:8]([C:25]([NH2:27])=[O:26])[CH:7]=[N:6][N:5]2[CH:28]=1.CC1(C)C(C)(C)OB([C:37]2[CH:38]=[N:39][N:40]([CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH:41]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N#N>CN(C)C=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[C:25]([C:8]1[CH:7]=[N:6][N:5]2[CH:28]=[C:2]([C:37]3[CH:38]=[N:39][N:40]([CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH:41]=3)[CH:3]=[C:4]2[C:9]=1[NH:10][C@H:11]1[C@@H:15]([CH3:16])[CH2:14][N:13]([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][N:18]=2)[CH2:12]1)(=[O:26])[NH2:27]

Participants

9

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 162183851-(Ethoxycarbonylmethyl)-1H-pyrazole-4-boronic acid pinacol esterHCID 682913406-bromo-4-(((3S,4S)-1-(5-cyanopyridin-2-yl)-4-methylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

Product 1

HCID 68291422ethyl 2-(4-(3-carbamoyl-4-(((3S,4S)-1-(5-cyanopyridin-2-yl)-4-methylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazin-6-yl)-1H-pyrazol-1-yl)acetateYield 119.6%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A stirred solution of 6-bromo-4-(((3S,4S)-1-(5-cyanopyridin-2-yl)-4-methylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (55 mg, 0.125 mmol, from Step 1 of Example 158), ethyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)acetate (70.0 mg, 0.250 mmol), potassium phosphate tribasic (80 mg, 0.375 mmol), palladium(II) acetate (5.61 mg, 0.025 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene (12.00 mg, 0.025 mmol) in N,N-dimethylformamide (1 mL) was degassed by vacuum-N2 refill cycle twice. The sealed tube was then heated at 100° C. for 40 min. The reaction mixture was diluted with water and filtered. The filter cake was washed with water and dried under vacuum to give crude ethyl 2-(4-(3-carbamoyl-4-(((3S,4S)-1-(5-cyanopyridin-2-yl)-4-methylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazin-6-yl)-1H-pyrazol-1-yl)acetate (76.8 mg), which was used in the next step without purification.

Workup

  1. filtrationfiltered
  2. washThe filter cake was washed with water
  3. customdried under vacuum

Sources & evidence

ORD record
ord-c124aeb515104551adfadfe154284888
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

Loading…