Triethylamine → methyl 1-(5-bromo-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-(tert-butoxycarbonylamino)piperidine-4-carboxylate

HRID 423079

Reaction equation

HRID 423079 reaction equation
C(N(CC)CC)C.[Br:8][C:9]1[C:17]2[C:16](Cl)=[N:15][CH:14]=[N:13][C:12]=2[N:11]([S:19]([C:22]2[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH:10]=1.[C:29]([O:33][C:34]([NH:36][C:37]1([C:43]([O:45][CH3:46])=[O:44])[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)=[O:35])([CH3:32])([CH3:31])[CH3:30]>CC(N(C)C)=O>[Br:8][C:9]1[C:17]2[C:16]([N:40]3[CH2:41][CH2:42][C:37]([NH:36][C:34]([O:33][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:35])([C:43]([O:45][CH3:46])=[O:44])[CH2:38][CH2:39]3)=[N:15][CH:14]=[N:13][C:12]=2[N:11]([S:19]([C:22]2[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 14537079Methyl 4-(((1,1-dimethylethoxy)carbonyl)amino)-4-piperidinecarboxylateHCID 577502825-Bromo-4-Chloro-7-Tosyl-7H-Pyrrolo[2,3-D]Pyrimidine2×

Product 1

HCID 57750316methyl 1-(5-bromo-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-(tert-butoxycarbonylamino)piperidine-4-carboxylateYield 69.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
70 °C

Procedure

Triethylamine (3.55 mL, 25.45 mmol) was added to 5-bromo-4-chloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine (Intermediate 61) (3.28 g, 8.48 mmol) and methyl 4-(tert-butoxycarbonylamino)piperidine-4-carboxylate (WO2008075109) (3.07 g, 11.88 mmol) in DMA (50 mL) at 20° C. The resulting suspension was stirred at 70° C. for 2 hours. The reaction mixture was concentrated and diluted with EtOAc (200 mL), and washed sequentially with water (75 mL) and saturated brine (75 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 30 to 70% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 1-(5-bromo-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-(tert-butoxycarbonylamino)piperidine-4-carboxylate (3.60 g, 69.7%) as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with EtOAc (200 mL)
  3. washwashed sequentially with water (75 mL) and saturated brine (75 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product
  8. customThe crude product was purified by flash silica chromatography, elution gradient 30 to 70% EtOAc in isohexane
  9. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-7922988e72024c27b29e21c8602c3d8a
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Linked notes

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