Carbon tetrabromide → 3-(bromomethyl)-1-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutylacetonitrile

HRID 1692951Notes

Reaction equation

HRID 1692951 reaction equation
O[CH2:2][CH:3]1[CH2:6][C:5]([CH2:29][C:30]#[N:31])([N:7]2[CH:11]=[C:10]([C:12]3[C:13]4[CH:20]=[CH:19][N:18]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:14]=4[N:15]=[CH:16][N:17]=3)[CH:9]=[N:8]2)[CH2:4]1.C(Br)(Br)(Br)[Br:33].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])(O)=O.[Na+]>CN(C=O)C.O>[Br:33][CH2:2][CH:3]1[CH2:6][C:5]([CH2:29][C:30]#[N:31])([N:7]2[CH:11]=[C:10]([C:12]3[C:13]4[CH:20]=[CH:19][N:18]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:14]=4[N:15]=[CH:16][N:17]=3)[CH:9]=[N:8]2)[CH2:4]1

Participants

7

Reactant 4

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 670172063-(hydroxymethyl)-1-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutylacetonitrile

Product 1

HCID 670172173-(bromomethyl)-1-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutylacetonitrileYield 87%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To an ice-cooled mixture of 3-(hydroxymethyl)-1-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutylacetonitrile (1.0 g, 0.0023 mol) and carbon tetrabromide (1.1 g, 0.0034 mol) in DMF (7 mL) was added triphenylphosphine (0.90 g, 0.0034 mol) and the mixture was stirred at this temp. for 30 min. To the resulting dark brown solution was added saturated aq. NaHCO3 (5 mL) followed by water (5 mL) and the mixture was extracted with dichloromethane. The organic layers were combined, washed with water, dried over Na2SO4, concentrated and purified with combiflash (silica gel, 0-40% EtOAc/Hex) to give the desired product (1.0 g, 87%) as light yellow solid. LCMS calculated for C22H30BrN6OSi(M+H)+: 501.1: Found: 501.3.

Workup

  1. extractionthe mixture was extracted with dichloromethane
  2. washwashed with water
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. custompurified with combiflash (silica gel, 0-40% EtOAc/Hex)

Sources & evidence

ORD record
ord-baf0cc52844f4680ae2386d87344ee01
Source dataset
uspto-grants-2012_04
Patent number
US08158616B2

Reaction notes

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