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

HRID 2391586ノート

反応式

HRID 2391586 の反応式
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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
130 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e2b64ddc714a4c85bfc0509688f0926c
出典データセット
uspto-grants-2012_09
特許番号
US08273890B2

反応ノート

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