N-(3-aminobenzyl)-2,2,2-trifluoroacetamide → 2,2,2-Trifluoro-N-[(3-{[4-(2-{3-[(3-thienylacetyl)amino]phenyl}pyrazolo-[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}phenyl)methyl]acetamide

HRID 1157595Notes

Reaction equation

HRID 1157595 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][NH:9][C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:6][CH:7]=1.Cl[C:17]1[N:22]=[C:21]([C:23]2[C:24]([C:32]3[CH:33]=[C:34]([NH:38][C:39](=[O:46])[CH2:40][C:41]4[CH:45]=[CH:44][S:43][CH:42]=4)[CH:35]=[CH:36][CH:37]=3)=[N:25][N:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=23)[CH:20]=[CH:19][N:18]=1>CC(O)C.Cl.C(Cl)Cl>[F:14][C:11]([F:12])([F:13])[C:10]([NH:9][CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:17]2[N:22]=[C:21]([C:23]3[C:24]([C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([NH:38][C:39](=[O:46])[CH2:40][C:41]5[CH:45]=[CH:44][S:43][CH:42]=5)[CH:33]=4)=[N:25][N:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=34)[CH:20]=[CH:19][N:18]=2)[CH:3]=1)=[O:15]

Participants

6

Reactant 2

HCID 21131928N-(3-aminobenzyl)-2,2,2-trifluoroacetamideHCID 57737204N-{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(3-thienyl)acetamide

Product 1

HCID 577372022,2,2-Trifluoro-N-[(3-{[4-(2-{3-[(3-thienylacetyl)amino]phenyl}pyrazolo-[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}phenyl)methyl]acetamideYield 53%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of N-[(3-aminophenyl)methyl]-2,2,2-trifluoroacetamide (73 mg, 0.34 mmol) and N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(3-thienyl)acetamide (120 mg, 0.27 mmol) in i-PrOH (4 mL) was acidified with 3 drops of 12 N HCl and stirred at 80° C. overnight. After 16 h, the reaction mixture was diluted with DCM, washed with saturated aqueous NaHCO3, dried over Na2SO4, and adsorbed onto silica gel. The crude product was purified by column chromatography to generate the title compound in 53% yield. 1H NMR (400 MHz, d6-DMSO) δ 10.28 (s, 1H), 9.98 (t, 1H), 9.63 (s, 1H), 8.83 (d, J=6.9 Hz, 1H), 8.52 (d, J=9.0 Hz, 1H), 8.24 (d, J=5.1 Hz, 1H), 7.90 (s, 1H), 7.63 (s, 1H), 7.75 (d, J=9.0 Hz, 1H), 7.71 (s, 1H), 7.67 (d, J=8.2 Hz, 1H), 7.47-7.49 (m, 2H), 7.42 (t, J=7.9 Hz, 1H), 7.32 (d, J=2.2 Hz, 1H), 7.26 (d, J=9.1 Hz, 1H), 7.22 (d, J=7.9 Hz, 1H), 7.08-7.13 (m, 2H), 6.85 (d, J=7.7 Hz, 1H), 6.51 (d, J=5.1 Hz, 1H), 4.35 (d, J=5.9 Hz, 2H), 3.66 (s, 2H). ES-LC/MS m/z=628 [M+H]+.

Workup

  1. waitAfter 16 h
  2. washwashed with saturated aqueous NaHCO3
  3. dry with materialdried over Na2SO4
  4. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-87c15a6c145941778144e3f26a02e154
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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