Ammonium Chloride → 2,5-dichloro-3-{[5-chloro-1-({1-(4-methoxybenzyl)-6-[(4-methoxybenzyl)amino]-1H-pyrazolo[3,4-b]pyridin-3-yl}methyl)-1H-1,2,3-benzotriazol-4-yl]oxy}benzonitrile

HRID 505556노트

반응식

HRID 505556 반응식
[Cl:1][C:2]1[C:9]([O:10][C:11]2[C:19]3[N:18]=[N:17][NH:16][C:15]=3[CH:14]=[CH:13][C:12]=2[Cl:20])=[CH:8][C:7]([Cl:21])=[CH:6][C:3]=1[C:4]#[N:5].CC(C)([O-])C.[Li+].Cl[CH2:29][C:30]1[C:38]2[C:33](=[N:34][C:35]([NH:39][CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=3)=[CH:36][CH:37]=2)[N:32]([CH2:49][C:50]2[CH:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][CH:51]=2)[N:31]=1.[Cl-].[NH4+]>CN(C=O)C>[Cl:1][C:2]1[C:9]([O:10][C:11]2[C:19]3[N:18]=[N:17][N:16]([CH2:29][C:30]4[C:38]5[C:33](=[N:34][C:35]([NH:39][CH2:40][C:41]6[CH:42]=[CH:43][C:44]([O:47][CH3:48])=[CH:45][CH:46]=6)=[CH:36][CH:37]=5)[N:32]([CH2:49][C:50]5[CH:51]=[CH:52][C:53]([O:56][CH3:57])=[CH:54][CH:55]=5)[N:31]=4)[C:15]=3[CH:14]=[CH:13][C:12]=2[Cl:20])=[CH:8][C:7]([Cl:21])=[CH:6][C:3]=1[C:4]#[N:5]

참가 물질

6

반응물 4

HCID 25517Ammonium ChlorideHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 568336463-(Chloromethyl)-N,1-bis(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amineHCID 178509931HCID 178509931, 화합물

생성물 1

HCID 684280332,5-dichloro-3-{[5-chloro-1-({1-(4-methoxybenzyl)-6-[(4-methoxybenzyl)amino]-1H-pyrazolo[3,4-b]pyridin-3-yl}methyl)-1H-1,2,3-benzotriazol-4-yl]oxy}benzonitrile

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

2,5-dichloro-3-[(5-chloro-1H-1,2,3-benzotriazol-4-yl)oxy]benzonitrile (90 mg, 0.265 mmol) and lithium tert-butoxide (22 mg, 0.278 mmol) were dissolved in DMF (1 mL) and the solution stirred for 5 minutes at room temperature. The reaction mixture was cooled to 0° C. and 3-(chloromethyl)-N,1-bis(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amine (112 mg, 0.265 mmol) in DMF (1.5 mL) was added. After the addition, the solution was allowed to warm to room temperature and stirred for 16 hours, after which saturated aqueous ammonium chloride (1 mL) was added and the mixture was extracted with ethyl acetate (2×15 mL). The combined organic fractions were washed with water (3×15 mL). The combined aqueous layers were back-extracted with EtOAc (25 mL) and the extracts subsequently washed with water (3×15 mL). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (12 g) eluting with 0-40% EtOAc/hexanes to afford the title compound. LRMS (M+1)=726.3.

후처리

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. additionAfter the addition
  3. temperatureto warm to room temperature
  4. stirringstirred for 16 hours
  5. extractionthe mixture was extracted with ethyl acetate (2×15 mL)
  6. washThe combined organic fractions were washed with water (3×15 mL)
  7. extractionThe combined aqueous layers were back-extracted with EtOAc (25 mL)
  8. washthe extracts subsequently washed with water (3×15 mL)
  9. dry with materialThe combined organic fractions were dried (MgSO4)
  10. filtrationfiltered
  11. customthe solvent was evaporated under reduced pressure
  12. customThe resulting residue was purified by column chromatography on silica gel (12 g)
  13. washeluting with 0-40% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-d49d905b1c15406798a5b92e8435597f
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07781454B2

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