Hydrochloric Acid → Benzyl 3-(2-amino-6-{[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]-amino}pyrimidin-4-yl)piperidine-1-carboxylate

HRID 16430Notes

Reaction equation

HRID 16430 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH:8]2[CH2:13][CH2:12][CH2:11][N:10]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[CH2:9]2)[CH:5]=[C:4](Cl)[N:3]=1.[F:25][C:26]1[CH:27]=[C:28]([CH:30]=[CH:31][C:32]=1[O:33][C:34]1[CH:39]=[CH:38][N:37]=[C:36]2[NH:40][CH:41]=[CH:42][C:35]=12)[NH2:29].Cl.C(=O)(O)[O-].[Na+]>O.C(O)C>[NH2:1][C:2]1[N:7]=[C:6]([CH:8]2[CH2:13][CH2:12][CH2:11][N:10]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[CH2:9]2)[CH:5]=[C:4]([NH:29][C:28]2[CH:30]=[CH:31][C:32]([O:33][C:34]3[CH:39]=[CH:38][N:37]=[C:36]4[NH:40][CH:41]=[CH:42][C:35]=34)=[C:26]([F:25])[CH:27]=2)[N:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 160379654-((1H-Pyrrolo[2,3-B]pyridin-4-YL)oxy)-3-fluoroanilineHCID 58733388Benzyl 3-(2-amino-6-chloropyrimidin-4-yl)piperidine-1-carboxylate

Product 1

HCID 58733285Benzyl 3-(2-amino-6-{[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]-amino}pyrimidin-4-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

1.05 g (2.89 mmol) of benzyl 3-(2-amino-6-chloropyrimidin-4-yl)piperidine-1-carboxylate (from example LXXII) and 0.75 g (2.89 mmol) of [3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]amine (from example XIX) are suspended in 35 ml of water and 4 ml of ethanol. 0.29 ml (3.47 mmol) of 37% strength hydrochloric acid is added. The mixture is stirred at 100° C. for 18 hours. After cooling, the mixture is neutralized using a saturated aqueous sodium bicarbonate solution and extracted three times with ethyl acetate (in each case 30 ml). The organic phase is dried over anhydrous magnesium sulfate and concentrated. The residue is purified on a silica gel column using dichloromethane/methanol 20:1. This gives 1.38 g (86% of theory) of product.

Workup

  1. temperatureAfter cooling
  2. extractionextracted three times with ethyl acetate (in each case 30 ml)
  3. dry with materialThe organic phase is dried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue is purified on a silica gel column

Sources & evidence

ORD record
ord-abd1a743184646fcae19d5418e7397bb
Source dataset
uspto-grants-2010_06
Patent number
US07737153B2

Reaction notes

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