Sodium borohydride → tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate

HRID 423055

Reaction equation

HRID 423055 reaction equation
[BH4-].[Na+].[C:3]([O:7][C:8]([NH:10][C:11]1([C:26]([NH:28][CH:29]([C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=2)[CH2:30][C:31](OC)=[O:32])=[O:27])[CH2:16][CH2:15][N:14]([C:17]2[C:18]3[CH:25]=[CH:24][NH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH2:13][CH2:12]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>CCO.O>[Cl:41][C:38]1[CH:37]=[CH:36][C:35]([CH:29]([NH:28][C:26]([C:11]2([NH:10][C:8](=[O:9])[O:7][C:3]([CH3:5])([CH3:4])[CH3:6])[CH2:12][CH2:13][N:14]([C:17]3[C:18]4[CH:25]=[CH:24][NH:23][C:19]=4[N:20]=[CH:21][N:22]=3)[CH2:15][CH2:16]2)=[O:27])[CH2:30][CH2:31][OH:32])=[CH:40][CH:39]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 57750359methyl 3-(4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)-3-(4-chlorophenyl)propanoate2×

Product 1

HCID 57750387tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamateYield 30.1%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 702EthanolSolvent

Conditions

Temperature
20 °C

Procedure

Sodium borohydride (1.019 g, 26.93 mmol) was added in one portion to a stirred suspension of methyl 3-(4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)-3-(4-chlorophenyl)propanoate (Intermediate 35) (1.0 g, 1.80 mmol) dissolved in EtOH (400 mL) under argon. The resulting suspension was stirred at 20° C. for 70 hours. A few drops of water were added to quench the excess of hydride and the mixture stirred for 1 hour. The mixture was evaporated to dryness and the residue was partitioned between CH2Cl2 and water saturated with NaCl. The organic phase was dried and concentrated to provide crude product as white crystals. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in dichloromethane. The pure fractions were evaporated to dryness to afford tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (286 mg, 30.1%) as a white solid.

Workup

  1. customto quench the excess of hydride
  2. stirringthe mixture stirred for 1 hour
  3. customThe mixture was evaporated to dryness
  4. customthe residue was partitioned between CH2Cl2 and water saturated with NaCl
  5. customThe organic phase was dried
  6. concentrationconcentrated
  7. customto provide crude product as white crystals
  8. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in dichloromethane
  9. customThe pure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-31176b2569084376963103a80d864f8d
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Linked notes

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