N-{3-[3-(2-chloro-4-pyrimidinyl)-6-(methyloxy)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide → N-{3-[3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}-6-(methyloxy)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide

HRID 1157643Notes

Reaction equation

HRID 1157643 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:19]3[CH:20]=[C:21]([NH:25][C:26](=[O:31])[C:27]([F:30])([F:29])[F:28])[CH:22]=[CH:23][CH:24]=3)=[N:10][N:11]3[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.Cl.Cl.[NH2:34][C:35]1[CH:36]=[C:37]([O:41][CH2:42][CH2:43][N:44]([CH3:46])[CH3:45])[CH:38]=[CH:39][CH:40]=1>CC(O)C>[CH3:45][N:44]([CH3:46])[CH2:43][CH2:42][O:41][C:37]1[CH:36]=[C:35]([NH:34][C:2]2[N:7]=[C:6]([C:8]3[C:9]([C:19]4[CH:20]=[C:21]([NH:25][C:26](=[O:31])[C:27]([F:29])([F:28])[F:30])[CH:22]=[CH:23][CH:24]=4)=[N:10][N:11]4[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][C:12]=34)[CH:5]=[CH:4][N:3]=2)[CH:40]=[CH:39][CH:38]=1

Participants

4

Reactant 2

HCID 57737181N-{3-[3-(2-chloro-4-pyrimidinyl)-6-(methyloxy)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamideHCID 66649609[2-(3-Aminophenoxy)ethyl]dimethylamine dihydrochloride

Product 1

HCID 86631087N-{3-[3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}-6-(methyloxy)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

N-{3-[3-(2-chloro-4-pyrimidinyl)-6-(methyloxy)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide (0.26 g, 0.58 mmol) and {2-[(3-aminophenyl)oxy]ethyl}dimethylamine dihydrochloride (0.18 g, 0.70 mmol) were combined in i-PrOH (4 mL)) and microwaved for 15 min. at 160° C. The reaction mixture was concentrated to dryness to afford N-{3-[3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}-6-(methyloxy)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide as a brown solid. The solid was dissolved in THF (5 mL) and water (0.5 mL) and treated with 1N NaOH (3 mL) and stirred for 16 h at rt after which time the reaction was incomplete by LC/MS. 1N NaOH (1 mL) was added and the mixture heated at 40° C. for 2 h and then cooled to rt and diluted with DCM and water. The organic layer was washed with brine, dried over MgSO4 and concentrated to give the title compound as crude yellow solid (320 mg, >100%), which was used as such in Step C. ES-LC/MS m/z=496 [M+H]+.

Workup

  1. custommicrowaved for 15 min. at 160° C
  2. concentrationThe reaction mixture was concentrated to dryness

Sources & evidence

ORD record
ord-bcdc3c290d944ee9a432a04f6592c805
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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