Formaldehyde → 4-({3-Chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-6-(methylamino)-7-(4-pyrrolidin-1-ylpiperidin-1-yl)quinoline-3-carbonitrile

HRID 269780노트

반응식

HRID 269780 반응식
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N:12]1[CH2:17][CH2:16][CH:15]([N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[CH2:14][CH2:13]1)[N:8]=[CH:7][C:6]([C:23]#[N:24])=[C:5]2[NH:25][C:26]1[CH:31]=[CH:30][C:29]([S:32][C:33]2[N:34]([CH3:38])[CH:35]=[CH:36][N:37]=2)=[C:28]([Cl:39])[CH:27]=1.C=O.[C:42]([BH3-])#N.[Na+]>C(O)(=O)C.C(O)C>[Cl:39][C:28]1[CH:27]=[C:26]([NH:25][C:5]2[C:4]3[C:9](=[CH:10][C:11]([N:12]4[CH2:13][CH2:14][CH:15]([N:18]5[CH2:19][CH2:20][CH2:21][CH2:22]5)[CH2:16][CH2:17]4)=[C:2]([NH:1][CH3:42])[CH:3]=3)[N:8]=[CH:7][C:6]=2[C:23]#[N:24])[CH:31]=[CH:30][C:29]=1[S:32][C:33]1[N:34]([CH3:38])[CH:35]=[CH:36][N:37]=1

참가 물질

6

반응물 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 68460429HCID 68460429, 화합물

생성물 1

HCID 684588494-({3-Chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-6-(methylamino)-7-(4-pyrrolidin-1-ylpiperidin-1-yl)quinoline-3-carbonitrile수율 50.1%

시약·촉매·용매 2

HCID 176Acetic Acid촉매HCID 702Ethanol용매

실험 절차

A mixture of 130 mg (0.23 mmol) of 6-amino-4-[3-chloro-4-(1-methyl-1H-imidazole-2-ylsulfanyl)phenylamino]-7-(4-pyrrolidin-1-yl-piperidin-1-yl)quinoline-3-carbonitrile, 12.0 mg (0.4 mmol) of paraformaldehyde, 25.0 mg (0.39 mmol) of sodium cyanoborohydride and 2 drops of acetic acid in 15 mL of ethanol is heated under reflux for 8 hours. The mixture is cooled to room temperature and solvent removed in vacuo. A 12 mL solution of 1N sodium hydroxide is added to the residue, and the mixture is stirred. A crude solid is collected by filtration, washed with water and dried. Purification by silica gel chromatography (gradient 95:5 methylene chloride/methanol to 4:1 methylene chloride/methanol) gives 66.0 mg of the 4-({3-Chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-6-(methylamino)-7-(4-pyrrolidin-1-ylpiperidin-1-yl)quinoline-3-carbonitrile as an yellow solid, mp 242-250° C.

후처리

  1. temperatureis heated
  2. temperatureunder reflux for 8 hours
  3. customsolvent removed in vacuo
  4. additionA 12 mL solution of 1N sodium hydroxide is added to the residue
  5. filtrationA crude solid is collected by filtration
  6. washwashed with water
  7. customdried
  8. customPurification by silica gel chromatography (gradient 95:5 methylene chloride/methanol to 4:1 methylene chloride/methanol)

출처 및 근거

ORD 기록
ord-8fd031f4f97f4e779aea60ed8b206d80
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07449460B2

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