Tris(hydroxymethyl)aminomethane → 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

HRID 1157536

反応式

HRID 1157536 の反応式
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[C:19]([NH2:23])[CH:20]=[CH:21][CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.[S:24]1[CH:28]=[CH:27][CH:26]=[C:25]1[CH2:29][C:30](Cl)=[O:31].[CH2:33](O)[C:34](N)([CH2:37][OH:38])[CH2:35]O>C1COCC1>[O:38]1[C:37]([C:34]2[CH:35]=[C:6]([NH:7][C:2]3[N:7]=[C:6]([C:8]4[C:9]([C:17]5[CH:18]=[C:19]([NH:23][C:30](=[O:31])[CH2:29][C:25]6[S:24][CH:28]=[CH:27][CH:26]=6)[CH:20]=[CH:21][CH:22]=5)=[N:10][N:11]5[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=45)[CH:5]=[CH:4][N:3]=3)[CH:8]=[CH:12][CH:33]=2)=[CH:4][N:3]=[CH:2]1

参加物

5

反応物 3

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 1623622-Thiopheneacetyl chlorideHCID 57737164{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}amine

生成物 1

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)acetamide収率 98%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirred solution of {3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}amine (200 mg, 0.62 mmol) and TEA (64 mg, 0.63 mmol) in THF (25 mL) was added dropwise 2-thiopheneacetyl chloride (118 mg, 0.73 mmol). After stirring for 20 min., 15 min. LC/MS analysis indicated the reaction was complete and several equivalents of PS-trisamine were added and the mixture was stirred for 16 h followed by addition of 25 mg of TEA. The mixture was then filtered and the resin washed well with THF. The filtrate was concentrated and the crude partitioned between water and DCM. The layers were separated, and the aqueous was extracted with DCM. The organics were combined, filtered over MgSO4, filtered, reduced in vacuo to yield the title compound (270 mg, 98% yield). 1H NMR (400 MHz, d6-DMSO) δ 10.41 (s, 1H), 8.92 (d, J=6.9 Hz, 1H), 8.48 (d, J=5.3 Hz, 1H), 8.43 (d, J=9.0 Hz, 1H), 7.91 (s, 1H), 7.78 (d, J=8.1 Hz, 1H), 7.67 (t, J=7.3 Hz, 1H), 7.49 (t, J=7.9 Hz, 1H), 7.40-7.43 (m, 1H), 7.31 (d, J=6.8 Hz, 1H), 7.24 (dt, J=1.1, 6.8 Hz, 1H), 7.07 (d, J=55 Hz, 1H), 6.99-7.01 (m, 2H), 3.91 (s, 2H) ppm. ES-LC/MS m/z=446, 448 [M+H]+.

後処理

  1. stirringthe mixture was stirred for 16 h
  2. filtrationThe mixture was then filtered
  3. washthe resin washed well with THF
  4. concentrationThe filtrate was concentrated
  5. customthe crude partitioned between water and DCM
  6. customThe layers were separated
  7. extractionthe aqueous was extracted with DCM
  8. filtrationfiltered over MgSO4
  9. filtrationfiltered

出典と根拠

ORDレコード
ord-d39a41c80e9544ba838ce1f4919da86c
出典データセット
uspto-grants-2010_10
特許番号
US07807673B2

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