Tris(hydroxymethyl)aminomethane → 2-Chloro-5-fluoro-N-(3-{3-[2-(3-fluoro-phenylamino)-pyrimidin-4-yl]-pyrazolo[1,5-a]pyridin-2-yl}-phenyl)-benzamide

HRID 1159885노트

반응식

HRID 1159885 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:31][C:32]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:33]=1[C:34](Cl)=[O:35].C(O)C(N)(CO)CO.CCN(CC)CC>C1COCC1>[Cl:31][C:32]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:33]=1[C:34]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:3]=1)=[O:35]

참가 물질

6

반응물 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 8471TriethylamineHCID 27575402-Chloro-5-fluorobenzoyl chlorideHCID 595114034-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-fluorophenyl)-2-pyrimidinamine

생성물 1

HCID 595137492-Chloro-5-fluoro-N-(3-{3-[2-(3-fluoro-phenylamino)-pyrimidin-4-yl]-pyrazolo[1,5-a]pyridin-2-yl}-phenyl)-benzamide수율 46.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of {4-[2-(3-amino-phenyl)-pyrazolo[1,5-a]pyridin-3-yl]-pyrimidin-2-yl}-(3-fluoro-phenyl)-amine (80 mg, 0.20 mmol) in 2 mL THF was added 2-chloro-5-fluorobenzoyl chloride (26 μL, 0.22 mmol). When LC/MS indicated the reaction was complete, several equivalents of PS-trisamine were added and the mixture was stirred for 16 h. Et3N was added if necessary to get the reaction into solution. The mixture was filtered and the resin washed well with THF. The filtrate was concentrated and triturated with DCM to give the title compound (51 mg, 46%). 1H NMR (400 MHz, d6-DMSO) δ 10.66 (s, 1H), 9.78 (s, 1H), 8.84 (d, J=6.8 Hz, 1H), 8.45 (d, J=8.8 Hz, 1H), 8.30 (d, J=5.2 Hz, 1H), 8.01 (s, 1H), 7.80-7.74 (m, 2H), 7.61-7.42 (m, 5H), 7.39-7.32 (m, 2H), 7.26-7.20 (m, 1H), 7.11 (t, J=6.4 Hz, 1H), 6.72-6.67 (m, 1H), 6.57 (d, J=5.2 Hz, 1H) ppm. MS (ESI) m/z=553 [M+H]+.

후처리

  1. customto get
  2. customthe reaction into solution
  3. filtrationThe mixture was filtered
  4. washthe resin washed well with THF
  5. concentrationThe filtrate was concentrated
  6. customtriturated with DCM

출처 및 근거

ORD 기록
ord-4104fe05f6f8457485ecf461f22f3bc2
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07812022B2

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