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

HRID 1692915Notes

Reaction equation

HRID 1692915 reaction equation
[C:1]([CH2:3][C:4]1([N:12]2[CH:16]=[C:15]([C:17]3[C:18]4[CH:25]=[CH:24][N:23]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:19]=4[N:20]=[CH:21][N:22]=3)[CH:14]=[N:13]2)[CH2:7][CH:6]([C:8](OC)=[O:9])[CH2:5]1)#[N:2].O1CCCC1.[BH4-].[Li+]>CO>[OH:9][CH2:8][CH:6]1[CH2:7][C:4]([CH2:3][C:1]#[N:2])([N:12]2[CH:16]=[C:15]([C:17]3[C:18]4[CH:25]=[CH:24][N:23]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:31])([CH3:33])[CH3:32])[C:19]=4[N:20]=[CH:21][N:22]=3)[CH:14]=[N:13]2)[CH2:5]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 4148881Lithium borohydrideHCID 67017201methyl 3-(cyanomethyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutanecarboxylate

Product 1

HCID 670172063-(hydroxymethyl)-1-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutylacetonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of methyl 3-(cyanomethyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutanecarboxylate (7.0 g, 0.015 mol) in tetrahydrofuran (100 mL, 1 mol) was added lithium tetrahydroborate (0.327 g, 0.0150 mol) at 0° C. The reaction was then heated at 50° C. for 3 h. To the reaction was added 60 mL of methanol. The resulting mixture was heated at 50° C. for another 15 min, then evaporated to dryness. The residue was treated with 1 N HCl, then neutralized with solid sodium bicarbonate, extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate and evaporated to dryness. The residue was purified on silica gel, eluting with 0 to 100% EtOAc, to give the desired product as cis- and trans-mixture (5.85 g, 88.91%). LCMS calculated for C22H31N6O2Si(M+H)+: 439.2; Found: 439.4.

Workup

  1. temperatureThe resulting mixture was heated at 50° C. for another 15 min
  2. customevaporated to dryness
  3. additionThe residue was treated with 1 N HCl
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. customevaporated to dryness
  8. customThe residue was purified on silica gel
  9. washeluting with 0 to 100% EtOAc

Sources & evidence

ORD record
ord-f60900ea81554745b9488314fd186932
Source dataset
uspto-grants-2012_04
Patent number
US08158616B2

Reaction notes

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