N-{3-[3-(2-{[3-(1,3-Oxazol-5-yl)phenyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide → N-{3-[3-(2-{[3-({[2-(Dimethylamino)ethyl]amino}methyl)phenyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide

HRID 1157586Notes

Reaction equation

HRID 1157586 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]([CH2:16][CH2:17][N:18]([CH3:20])[CH3:19])C(=O)C(F)(F)F)[CH:5]=[CH:6][CH:7]=1.O1C(C2C=C(N[C:33]3[N:38]=[C:37]([C:39]4[C:40]([C:48]5[CH:49]=[C:50]([NH:54][C:55](=[O:62])[CH2:56][C:57]6[S:58][CH:59]=[CH:60][CH:61]=6)[CH:51]=[CH:52][CH:53]=5)=[N:41][N:42]5[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=45)[CH:36]=[CH:35][N:34]=3)C=CC=2)=CN=C1>CC(O)C.Cl.C(Cl)Cl>[CH3:20][N:18]([CH3:19])[CH2:17][CH2:16][NH:9][CH2:8][C:4]1[CH:3]=[C:2]([NH:1][C:33]2[N:38]=[C:37]([C:39]3[C:40]([C:48]4[CH:49]=[C:50]([NH:54][C:55](=[O:62])[CH2:56][C:57]5[S:58][CH:59]=[CH:60][CH:61]=5)[CH:51]=[CH:52][CH:53]=4)=[N:41][N:42]4[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=34)[CH:36]=[CH:35][N:34]=2)[CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 2

HCID 57737194N-{3-[3-(2-{[3-(1,3-Oxazol-5-yl)phenyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamideHCID 59511436HCID 59511436, compound

Product 1

HCID 57737176N-{3-[3-(2-{[3-({[2-(Dimethylamino)ethyl]amino}methyl)phenyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamideYield 66%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
180 °C

Procedure

A suspension of N-[(3-aminophenyl)methyl]-N-[2-(dimethylamino)ethyl]-2,2,2-trifluoroacetamide (61 mg, 0.21 mmol) and N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide (75 mg, 0.17 mmol) (see Example 2, Step B) in i-PrOH (3 mL) was acidified with 3 drops of 12 N HCl and heated in a microwave for 25 min. at 180° C. The reaction mixture was then diluted with DCM, washed with 2 N NaOH, dried over Na2SO4, and adsorbed onto silica gel. The crude product was purified by column chromatography to generate the title compound in 66% yield. 1H NMR (400 MHz, CDCl3) δ 8.47 (d, J=6.8 Hz, 1H), 8.36 (d, J=8.8 Hz, 1H), 8.16 (d, J=5.1 Hz, 1H), 7.80 (d, J=7.2 Hz, 1H), 7.73 (s, 1H), 7.53-7.61 (m, 3H), 7.32-7.45 (m, 4H), 7.01 (s, 2H), 6.90 (t, J=6.6 Hz, 1H), 6.55 (d, J=5.1 Hz, 1H), 3.94 (s, 2H), 3.79 (s, 2H), 2.70 (t, J=5.8 Hz, 2H), 2.42 (t, J=5.9 Hz, 2H), 2.18 (s, 6H). ES-LC/MS m/z=603 [M+H]+.

Workup

  1. washwashed with 2 N NaOH
  2. dry with materialdried over Na2SO4
  3. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-4c449f9359bd4813a202be2da7555bab
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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