Hydrochloric Acid → 5-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-methylnicotinamide

HRID 1986864

반응식

HRID 1986864 반응식
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[N:11][C:12]3[N:13]([N:15]=[CH:16][C:17]=3[C:18]3[CH:19]=[N:20][CH:21]=[C:22]([CH:28]=3)[C:23](OCC)=[O:24])[CH:14]=2)=[CH:5][CH:4]=1.[OH-].[Na+].Cl.C(Cl)(=O)C(Cl)=O.Cl.CN.[CH:41]([N:44](CC)C(C)C)(C)C>CC(O)(C)C.COCCOC.ClCCl.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:10]=[N:11][C:12]3[N:13]([N:15]=[CH:16][C:17]=3[C:18]3[CH:19]=[N:20][CH:21]=[C:22]([CH:28]=3)[C:23]([NH:44][CH3:41])=[O:24])[CH:14]=2)=[CH:7][CH:8]=1

참가 물질

11

반응물 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 57722617Ethyl 5-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]nicotinate

생성물 1

HCID 98851835-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-methylnicotinamide

시약·촉매·용매 4

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회HCID 6386tert-Butanol용매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
23 °C

실험 절차

A mixture of ethyl 5-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]nicotinate (2-2, 150 mg, 0.40 mmol, 1 equiv) and aqueous sodium hydroxide solution (1N, 1.0 mL), 1.0 mmol, 2.5 equiv) in a mixture of t-BuOH (2 mL) and DME (2 mL) was heated at reflux for 1 hour. The reaction mixture was allowed to cool to 23° C., and then it was acidified with aqueous 1 N hydrogen chloride solution. The precipitate was filtered, washed with water, and air dried. Oxalyl chloride (150 TL, 1.7 mmol, 4.3 equiv) followed by a catalytic amount of DMF (4 TL) was then added to a suspension of the filtered solid in dichloromethane (10 mL), and the resulting mixture was stirred for 30 minutes, then concentrated. A suspension of one-tenth of this residue (approximately 15 mg, 0.040 mmol), methylamine hydrochloride (27 mg, 0.40 mmol, 10 equiv) and N,N-diisopropylethylamine (200 TL, 1.1 mmol, 30 equiv) in dichloromethane (3 mL) was stirred at 23° C. for 30 minutes. The reaction mixture was partitioned between half-saturated aqueous sodium bicarbonate solution. The organic layer was dried over sodium sulfate and concentrated. The residue was suspended in methanol (3 mL) and filtered to give 5-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-methylnicotinamide (2-3) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.49 (d, 1H, J=2.2 Hz), 9.45 (d, 1H, J=2.2 Hz), 9.12 (d, 1H, J=2.2 Hz), 8.91 (s, 1H), 8.88 (t, 1H, J=2.0 Hz), 8.83 (d, 1H, J=2.0 Hz), 8.66 (br m, 1H), 7.84 (d, 2H, J=8.8 Hz), 7.10 (d, 2H, J=8.8 Hz), 3.82 (s, 3H), 2.84 (d, 3H, J=4.4 Hz).

후처리

  1. temperaturewas heated
  2. temperatureat reflux for 1 hour
  3. filtrationThe precipitate was filtered
  4. washwashed with water, and air
  5. customdried
  6. concentrationconcentrated
  7. stirringwas stirred at 23° C. for 30 minutes
  8. customThe reaction mixture was partitioned between half-saturated aqueous sodium bicarbonate solution
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. concentrationconcentrated
  11. filtrationfiltered

출처 및 근거

ORD 기록
ord-b135c0078b4c4bf2a4d510161882922f
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07550470B2

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