Dimethyl Sulfoxide → 3-Formyl-1-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]cyclobutylacetonitrile

HRID 1692917Notes

Reaction equation

HRID 1692917 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.C(Cl)Cl.[OH:14][CH2:15][CH:16]1[CH2:19][C:18]([CH2:42][C:43]#[N:44])([N:20]2[CH:24]=[C:23]([C:25]3[C:26]4[CH:33]=[CH:32][N:31]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[C:27]=4[N:28]=[CH:29][N:30]=3)[CH:22]=[N:21]2)[CH2:17]1.C(N(CC)CC)C>>[CH:15]([CH:16]1[CH2:17][C:18]([CH2:42][C:43]#[N:44])([N:20]2[CH:24]=[C:23]([C:25]3[C:26]4[CH:33]=[CH:32][N:31]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:39])([CH3:41])[CH3:40])[C:27]=4[N:28]=[CH:29][N:30]=3)[CH:22]=[N:21]2)[CH2:19]1)=[O:14]

Participants

6

Reactant 5

HCID 679Dimethyl SulfoxideHCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 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 872378153-Formyl-1-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]cyclobutylacetonitrileYield 86.4%

Procedure

Dimethyl sulfoxide (0.194 mL, 0.00274 mol) was added to a solution of oxalyl chloride (0.145 mL, 0.00171 mol) in methylene chloride (6.384 mL, 0.09959 mol) at −78° C. After 10 min, 3-(hydroxymethyl)-1-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutylacetonitrile (0.500 g, 0.00114 mol) in methylene chloride (12.77 mL, 0.1992 mol) was added and the resultant mixture was stirred at −78° C. for 30 min. Triethylamine (0.794 mL, 0.00570 mol) was then added and the mixture was stirred for 5 h with the temperature allowed to gradually warm up to rt. After quenching with water, the mixture was extracted with methylene chloride. The organic layers were combined, washed with brine, dried and evaporated to dry. The residue was purified on silica gel, eluting with 0 to 100% EtOAc in hexane, to give the desired aldehyde (430 mg, 86%). LCMS calculated for C22H29N6O2Si(M+H)+: 437.2; Found: 437.4.

Workup

  1. customAfter quenching with water
  2. extractionthe mixture was extracted with methylene chloride
  3. washwashed with brine
  4. customdried
  5. customevaporated
  6. customto dry
  7. customThe residue was purified on silica gel
  8. washeluting with 0 to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-94e20804a2084d2d9bf47d1dd5a342f8
Source dataset
uspto-grants-2012_04
Patent number
US08158616B2

Reaction notes

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