3-Thiophenacetic acid → N-[3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2-(3-thienyl)acetamide

HRID 1157583Notes

Reaction equation

HRID 1157583 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([O:30][CH2:31][CH2:32][N:33]([CH3:35])[CH3:34])[CH:25]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[S:36]1[CH:40]=[CH:39][C:38]([CH2:41][C:42](O)=[O:43])=[CH:37]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C1COCC1.C(Cl)Cl>[CH3:34][N:33]([CH3:35])[CH2:32][CH2:31][O:30][C:26]1[CH:25]=[C:24]([NH:23][C:19]2[N:18]=[C:17]([C:16]3[C:8]([C:4]4[CH:3]=[C:2]([NH:1][C:42](=[O:43])[CH2:41][C:38]5[CH:39]=[CH:40][S:36][CH:37]=5)[CH:7]=[CH:6][CH:5]=4)=[N:9][N:10]4[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=34)[CH:22]=[CH:21][N:20]=2)[CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 234043-Thiophenacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 577371664-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-{[2-(dimethylamino)ethyl]oxy}phenyl)-2-pyrimidinamine

Product 1

HCID 57737236N-[3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2-(3-thienyl)acetamideYield 72%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-{[2-(dimethylamino)ethyl]oxy}phenyl)-2-pyrimidinamine (140 mg, 0.3 mmol) in THF were added 3-thienylacetic acid (51 mg, 0.36 mmol), TEA (125 μL, 0.9 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (136 mg, 0.36 mmol). The reaction was stirred overnight at rt, after which the reaction mixture was diluted with DCM, washed with 5% aqueous Na2CO3, dried over Na2SO4, and adsorbed onto silica gel. The crude product was purified by column chromatography and lyophilized to generate the title compound in 72% yield. 1H NMR (400 MHz, d6-DMSO) δ 10.27 (s, 1H), 9.55 (s, 1H), 8.83 (d, J=6.7 Hz, 1H), 8.51 (d, J=8.8 Hz, 1H), 8.26 (d, J=5.1 Hz, 1H), 7.89 (s, 1H), 7.76 (d, J=8.1 Hz, 1H), 7.40-7.53 (m, 4H), 7.26-7.31 (m, 3H), 7.08-7.18 (m, 3H), 6.53 (d, J=8.2 Hz, 1H), 6.48 (d, J=5.3 Hz, 1H), 3.99 (t, J=5.7 Hz, 2H), 3.66 (s, 2H), 2.58 (t, J=5.9 Hz, 2H), 2.18 (s, 6H). ES-LC/MS m/z=588 [M+H]+.

Workup

  1. washwashed with 5% aqueous Na2CO3
  2. dry with materialdried over Na2SO4
  3. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-71a7d93995a44c8587ab197de3464673
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

Loading…