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

반응식

HRID 1157536 반응식
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

참가 물질

5

반응물 3

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

생성물 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)acetamide수율 98%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-d39a41c80e9544ba838ce1f4919da86c
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807673B2

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