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

HRID 1157589Notes

Reaction equation

HRID 1157589 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]([CH2:16][CH2:17][S:18]([CH3:21])(=[O:20])=[O:19])[C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:6][CH:7]=1.O1C(C2C=C(N[C:34]3[N:39]=[C:38]([C:40]4[C:41]([C:49]5[CH:50]=[C:51]([NH:55][C:56](=[O:63])[CH2:57][C:58]6[S:59][CH:60]=[CH:61][CH:62]=6)[CH:52]=[CH:53][CH:54]=5)=[N:42][N:43]5[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=45)[CH:37]=[CH:36][N:35]=3)C=CC=2)=CN=C1>CC(O)C.Cl.CCOC(C)=O>[F:13][C:11]([F:14])([F:12])[C:10]([N:9]([CH2:16][CH2:17][S:18]([CH3:21])(=[O:20])=[O:19])[CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:34]2[N:39]=[C:38]([C:40]3[C:41]([C:49]4[CH:54]=[CH:53][CH:52]=[C:51]([NH:55][C:56](=[O:63])[CH2:57][C:58]5[S:59][CH:60]=[CH:61][CH:62]=5)[CH:50]=4)=[N:42][N:43]4[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=34)[CH:37]=[CH:36][N:35]=2)[CH:3]=1)=[O:15]

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 59511431HCID 59511431, compound

Product 1

HCID 577372392,2,2-Trifluoro-N-[2-(methylsulfonyl)ethyl]-N-[(3-{[4-(2-{3-[(2-thienylacetyl)amino]phenyl}pyrazolo[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}phenyl)methyl]acetamideYield 63%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
180 °C

Procedure

A suspension of N-[(3-aminophenyl)methyl]-2,2,2-trifluoro-N-[2-(methylsulfonyl)ethyl]acetamide (68 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 2 drops of 12 N HCl and heated in a microwave for 15 min. at 180° C. The reaction mixture was then diluted with EtOAc, 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 63% yield. 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J=6.8 Hz, 1H), 8.31 (d, J=8.6 Hz, 1H), 8.22 (d, J=5.3 Hz, 1H), 7.67-7.80 (m, 2H), 7.56 (d, J=8.0 Hz, 1H), 7.26-7.39 (m, 4H), 7.17 (t, J=7.7 Hz, 1H), 7.05 (s, 1H), 6.94 (t, J=6.9 Hz, 1H), 6.88 (d, J=8.4 Hz, 1H), 6.62-6.64 (m, 2H), 6.53 (s, 1H), 4.68 (s, 2H), 3.96 (s, 2H), 3.72-3.75 (m, 2H), 3.16-3.24 (m, 2H), 2.90 (s, 3H). ES-LC/MS m/z=734 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-70b49502fec6435c84c57863315b42be
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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