Formamide → Apixaban

HRID 860839

反応式

HRID 860839 の反応式
C([O:3][C:4]([C:6]1[C:14]2[CH2:13][CH2:12][N:11]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][C:22]4=[O:27])=[CH:17][CH:16]=3)[C:10](=[O:28])[C:9]=2[N:8]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)[N:7]=1)=O)C.C([NH2:39])=O.CO[Na].O>CN(C=O)C.CO>[CH3:36][O:35][C:32]1[CH:31]=[CH:30][C:29]([N:8]2[C:9]3[C:10](=[O:28])[N:11]([C:15]4[CH:20]=[CH:19][C:18]([N:21]5[CH2:26][CH2:25][CH2:24][CH2:23][C:22]5=[O:27])=[CH:17][CH:16]=4)[CH2:12][CH2:13][C:14]=3[C:6]([C:4]([NH2:39])=[O:3])=[N:7]2)=[CH:34][CH:33]=1

参加物

7

反応物 4

HCID 713FormamideHCID 962WaterHCID 22240488ethyl 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxo-1-piperidinyl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylateHCID 178418582HCID 178418582、化合物

生成物 1

HCID 10182969Apixaban収率 71.1%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

実験手順

Method B. A solution of 1-(4-methoxy-phenyl)-7-oxo-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester (65, 977 mg, 2.0 mmol) in DMF (5 mL) was treated with formamide (901 mg, 0.8 mL, 20 mmol, 10.0 equiv) at room temperature, and the resulting reaction mixture was cooled down to 0–5C before being treated dropwise with a solution of MeONa (864 mg, 0.92 mL, 4.0 mmol, 2.0 equiv) in methanol at 0–5C. The resulting reaction mixture was stirred at 0–5° C. for 30 min before being gradually warmed up to room temperature for an additional 3 h. When HPLC and TLC showed the reaction was complete, the reaction mixture was slowly poured into water (20 mL). The resulting mixture was then stirred at room temperature for 1 h to precipitate the desired product. The solids were collected by filtration, washed with water (2×10 mL) and methyl tert-butyl ether (2×10 mL), dried in vacuo at 40–45° C. for 12 h to afford the crude desired 1-(4-methoxy-phenyl)-7-oxo-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid amide (62, 653 mg, 919 mg theoretical, 71%) as off-whit crystals. This product was found to be identical with the material prepared from method A.

後処理

  1. customthe resulting reaction mixture
  2. temperaturewas cooled down to 0–5C
  3. customThe resulting reaction mixture
  4. stirringThe resulting mixture was then stirred at room temperature for 1 h
  5. customto precipitate the desired product
  6. filtrationThe solids were collected by filtration
  7. washwashed with water (2×10 mL) and methyl tert-butyl ether (2×10 mL)
  8. customdried in vacuo at 40–45° C. for 12 h

出典と根拠

ORDレコード
ord-0e5db39cfd79428b8eb7820480bbda88
出典データセット
uspto-grants-2006_12
特許番号
US07153960B2

関連ノート

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