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 269780Notes

Reaction equation

HRID 269780 reaction equation
[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

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 68460429HCID 68460429, compound

Product 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-carbonitrileYield 50.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 702EthanolSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-8fd031f4f97f4e779aea60ed8b206d80
Source dataset
uspto-grants-2008_11
Patent number
US07449460B2

Reaction notes

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