Phosgene → methyl 4-[({[4-(8-azabicyclo[3.2.1]oct-8-yl)-3-(trifluoromethyl)benzyl]amino}carbonyl)amino]-1H-indazole-1-carboxylate

HRID 586080

반응식

HRID 586080 반응식
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[C:11]([O:13][CH3:14])=[O:12].[C:15](Cl)(Cl)=[O:16].[CH:19]12[N:26]([C:27]3[CH:34]=[CH:33][C:30]([CH2:31][NH2:32])=[CH:29][C:28]=3[C:35]([F:38])([F:37])[F:36])[CH:23]([CH2:24][CH2:25]1)[CH2:22][CH2:21][CH2:20]2>C1(C)C=CC=CC=1.C1COCC1>[CH:23]12[N:26]([C:27]3[CH:34]=[CH:33][C:30]([CH2:31][NH:32][C:15]([NH:1][C:2]4[CH:10]=[CH:9][CH:8]=[C:7]5[C:3]=4[CH:4]=[N:5][N:6]5[C:11]([O:13][CH3:14])=[O:12])=[O:16])=[CH:29][C:28]=3[C:35]([F:38])([F:36])[F:37])[CH:19]([CH2:25][CH2:24]1)[CH2:20][CH2:21][CH2:22]2

참가 물질

6

반응물 3

HCID 6371PhosgeneHCID 22032652methyl 4-amino-1H-indazole-1-carboxylateHCID 223376164-(8-Azabicyclo[3.2.1]oct-8-yl)-3-(trifluoromethyl)benzylamine

생성물 1

HCID 22337659methyl 4-[({[4-(8-azabicyclo[3.2.1]oct-8-yl)-3-(trifluoromethyl)benzyl]amino}carbonyl)amino]-1H-indazole-1-carboxylate

시약·촉매·용매 2

HCID 1140Toluene용매2회HCID 8028Tetrahydrofuran용매

실험 절차

Methyl 4-amino-1H-indazole-1-carboxylate (1.72 g, 9.00 mmol) in toluene (300 mL) was treated with phosgene in toluene (9.00 mL, approx. 20% w/w) via syringe. The mixture was heated at reflux for 3.5 hours, allowed to cool to ambient temperature, and concentrated under reduced pressure. The residue was taken up in diethyl ether and concentrated under reduced pressure. The residue was again taken up in diethyl ether (325 mL) followed by addition of triethylamine (10 mL). The mixture was stirred briefly and then filtered. An aliquot of the filtrate (150 mL, 4.14 mmol) was treated with 4-(8-azabicyclo[3.2.1]oct-8-yl)-3-(trifluoromethyl)benzylamine (1.03 g, 3.62 mmol) in THF (10 mL). After stirring for 2 hours, the mixture was concentrated under reduced pressure to approximately 30 mL and filtered. The filter cake was washed with diethyl ether:hexane (1:1) and dried under reduced pressure to provide the title compound. 1H NMR (300 MHz, DMSO-d6) δ 9.07 (s, 1H), 8.43 (s, 1H), 7.80 (d, 1H, J=7.8 Hz), 7.69 (d, 1H, J=8.1 Hz), 7.58 (t, 1H, J=2.0 Hz), 7.47 (m, 2H), 7.14 (d, 1H, J=8.1 Hz), 6.86 (t, 1H, J=5.8 Hz), 4.32 (d, 2H, J=5.8 Hz), 4.03 (s, 3H), 3.72 (m, 2H), 1.93 (m, 2H), 1.88-1.55 (m, 5H), 1.49 (m, 3H); MS (ESI) 502 (M+H)+.

후처리

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3.5 hours
  3. concentrationconcentrated under reduced pressure
  4. concentrationconcentrated under reduced pressure
  5. additionfollowed by addition of triethylamine (10 mL)
  6. filtrationfiltered
  7. stirringAfter stirring for 2 hours
  8. concentrationthe mixture was concentrated under reduced pressure to approximately 30 mL
  9. filtrationfiltered
  10. washThe filter cake was washed with diethyl ether:hexane (1:1)
  11. customdried under reduced pressure

출처 및 근거

ORD 기록
ord-955c85abd71142adbbae56131dd49d52
출처 데이터셋
uspto-grants-2005_08
특허 번호
US06933311B2

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