Formamide → 1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]phenyl}phenyl)-7-oxo-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxamide

HRID 860834노트

반응식

HRID 860834 반응식
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]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH2:27][NH:28][CH3:29])=[CH:17][CH:16]=3)[C:10](=[O:30])[C:9]=2[N:8]([C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[N:7]=1)=O)C.C([NH2:41])=O.CO[Na].O>CN(C=O)C.CO>[CH3:38][O:37][C:34]1[CH:35]=[CH:36][C:31]([N:8]2[C:9]3[C:10](=[O:30])[N:11]([C:15]4[CH:20]=[CH:19][C:18]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=5[CH2:27][NH:28][CH3:29])=[CH:17][CH:16]=4)[CH2:12][CH2:13][C:14]=3[C:6]([C:4]([NH2:41])=[O:3])=[N:7]2)=[CH:32][CH:33]=1

참가 물질

7

반응물 4

HCID 713FormamideHCID 962WaterHCID 223185241-(4-Methoxy-phenyl)-6-(2'-methylaminomethyl-biphenyl-4-yl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c)pyridine-3-carboxylic acid ethyl esterHCID 178418582HCID 178418582, 화합물

생성물 1

HCID 101167521-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]phenyl}phenyl)-7-oxo-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxamide수율 83%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6228Dimethylformamide용매

실험 절차

A solution of 1-(4-methoxy-phenyl)-6-(2′-methylaminomethyl-biphenyl-4-yl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester (57, 13.5 g, 26.4 mmol) in DMF (50 mL) was treated with formamide (8.32 g, 6.2 mL, 184.8 mmol, 7.0 equiv) at room temperature, and the resulting reaction mixture was cooled down to 0–5° C. before being treated dropwise with a solution of MeONa (8.6 g, 9.05 mL, 39.6 mmol, 1.5 equiv) in methanol at 0–5° C. 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 (600 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 (2×100 mL) and methyl tert-butyl ether (2×100 mL), dried in vacuo at 40–45° C. for 12 h to afford crude desired 1-(4-methoxy-phenyl)-6-(2′-methylaminomethyl-biphenyl-4-yl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid amide (58, 10.55 g, 12.71 g theoretical, 83%). This crude solids were subsequently recrystallized in a mixture of ethanol and methanol to afford the pure product. For 58, CIMS m/z 482 (M++H, C28H27N5O3).

후처리

  1. customthe resulting reaction mixture
  2. temperaturewas cooled down to 0–5° C.
  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 (2×100 mL) and methyl tert-butyl ether (2×100 mL)
  8. customdried in vacuo at 40–45° C. for 12 h

출처 및 근거

ORD 기록
ord-1e4942799f2b4303aed7f2b533055d1f
출처 데이터셋
uspto-grants-2006_12
특허 번호
US07153960B2

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