Ammonia → 5-(6-Methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxamide

HRID 2391586노트

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HRID 2391586 반응식
COC1[N:8]=CC2N(C3SC(C(OC)=O)=C(OCC4C=CC=CC=4C(F)(F)F)C=3)C=NC=2C=1.[CH3:33][O:34][C:35]1[N:40]=[CH:39][C:38]2[N:41]=[CH:42][N:43]([C:44]3[S:48][C:47]([C:49]([O:51]C)=O)=[C:46]([O:53][CH2:54][C:55]4[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=4[C:61]([F:64])([F:63])[F:62])[CH:45]=3)[C:37]=2[CH:36]=1.N>CO>[CH3:33][O:34][C:35]1[N:40]=[CH:39][C:38]2[N:41]=[CH:42][N:43]([C:44]3[S:48][C:47]([C:49]([NH2:8])=[O:51])=[C:46]([O:53][CH2:54][C:55]4[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=4[C:61]([F:62])([F:63])[F:64])[CH:45]=3)[C:37]=2[CH:36]=1

참가 물질

5

반응물 3

HCID 222AmmoniaHCID 68766502methyl 5-(6-methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylateHCID 68768085methyl 5-(6-methoxy-3H-imidazo[4,5-c]pyridin-3-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate

생성물 1

HCID 251530835-(6-Methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxamide

시약·촉매·용매 1

HCID 887Methanol용매

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온도
130 °C

실험 절차

A suspension of 140 mg of an isomeric mixture of methyl 5-(6-methoxy-3H-imidazo[4,5-c]pyridin-3-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate and methyl 5-(6-methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate (compounds B6a and B6b) in 20 ml of a saturated solution of ammonia in methanol was stirred in a microwave vial at 130° C. for 5 h in the microwave cavity. The reaction mixture was concentrated to dryness, the residue dissolved in 4 ml acetonitrile and 3 ml acidic buffer (KH2PO4, pH=2) and the isomers were separated and purified by preparative HPLC (acidic buffer/acetonitrile, 7/3 (v/v)). The acetonitrile was removed under vacuum and the aqueous solution was treated with NH4OH until pH 8-9 was reached. The aqueous solution was extracted with dichloromethane three times and the combined organic layers were dried and concentrated to dryness under vacuum to yield the title compound.

후처리

  1. concentrationThe reaction mixture was concentrated to dryness
  2. dissolutionthe residue dissolved in 4 ml acetonitrile
  3. custom3 ml acidic buffer (KH2PO4, pH=2) and the isomers were separated
  4. custompurified by preparative HPLC (acidic buffer/acetonitrile, 7/3 (v/v))
  5. customThe acetonitrile was removed under vacuum
  6. additionthe aqueous solution was treated with NH4OH until pH 8-9
  7. extractionThe aqueous solution was extracted with dichloromethane three times
  8. customthe combined organic layers were dried
  9. concentrationconcentrated to dryness under vacuum

출처 및 근거

ORD 기록
ord-e2b64ddc714a4c85bfc0509688f0926c
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08273890B2

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