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

HRID 1157592ノート

反応式

HRID 1157592 の反応式
[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.O1C(C2C=C(N[C:28]3[N:33]=[C:32]([C:34]4[C:35]([C:43]5[CH:44]=[C:45]([NH:49][C:50](=[O:57])[CH2:51][C:52]6[S:53][CH:54]=[CH:55][CH:56]=6)[CH:46]=[CH:47][CH:48]=5)=[N:36][N:37]5[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=45)[CH:31]=[CH:30][N:29]=3)C=CC=2)=CN=C1>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:28]2[N:33]=[C:32]([C:34]3[C:35]([C:43]4[CH:48]=[CH:47][CH:46]=[C:45]([NH:49][C:50](=[O:57])[CH2:51][C:52]5[S:53][CH:54]=[CH:55][CH:56]=5)[CH:44]=4)=[N:36][N:37]4[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=34)[CH:31]=[CH:30][N:29]=2)[CH:3]=1)=[O:15]

参加物

6

反応物 2

HCID 21131928N-(3-aminobenzyl)-2,2,2-trifluoroacetamideHCID 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)acetamide

生成物 1

HCID 577372032,2,2-Trifluoro-N-[(3-{[4-(2-{3-[(2-thienylacetyl)amino]phenyl}-pyrazolo[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}phenyl)methyl]acetamide収率 67%

試薬・触媒・溶媒 3

HCID 313Hydrochloric Acid触媒HCID 3776Isopropanol溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
180 °C

実験手順

A suspension of N-[(3-aminophenyl)methyl]-2,2,2-trifluoroacetamide (46 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 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 67% yield. 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J=6.8 Hz, 1H), 8.31 (d, J=9.1 Hz, 1H), 8.22 (d, J=5.2 Hz, 1H), 7.72-7.75 (m, 2H), 7.63 (s, 1H), 7.46 (d, J=8.3 Hz, 1H), 7.26-7.38 (m, 7H), 7.04 (s, 1H), 6.94 (m, 1H), 6.63 (d, J=5.4 Hz, 1H), 4.48 (d, J=5.7 Hz, 2H), 3.96 (s, 2H). ES-LC/MS m/z=628 [M+H]+.

後処理

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

出典と根拠

ORDレコード
ord-557c8ceabab04b84bf7b94a00b95b16a
出典データセット
uspto-grants-2010_10
特許番号
US07807673B2

反応ノート

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