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

HRID 1692935Notes

Reaction equation

HRID 1692935 reaction equation
[C:1]([CH2:3][C:4]1([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)[CH2:7][C:6]([C:14](OC(C)C)=[O:15])([C:8](OC(C)C)=[O:9])[CH2:5]1)#[N:2].O1CCCC1.[BH4-].[Li+].Cl.C([O-])(O)=O.[Na+]>CO>[OH:15][CH2:14][C:6]1([CH2:8][OH:9])[CH2:5][C:4]([CH2:3][C:1]#[N:2])([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]([CH3:40])([CH3:41])[CH3:39])[C:27]=4[N:28]=[CH:29][N:30]=3)[CH:22]=[N:21]2)[CH2:7]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 4148881Lithium borohydrideHCID 67279569diisopropyl 3-(cyanomethyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutane-1,1-dicarboxylate

Product 1

HCID 670172033,3-bis(hydroxymethyl)-1-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutylacetonitrileYield 61.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

Diisopropyl 3-(cyanomethyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutane-1,1-dicarboxylate (0.3 g, 0.5 mmol) was dissolved in tetrahydrofuran (15 mL, 180 mmol) and lithium tetrahydroborate (0.017 g, 0.77 mmol) was added at 0° C. The reaction was then heated to 50° C. for 30 min. To the reaction was added MeOH (10 mL). The reaction was held at 50° C. for 15 min, then stripped to near dryness. The residue was treated with 1N HCl, then neutralized with solid NaHCO3. The mixture was partitioned between water and EtOAc. The phases were separated and the aq. phase was washed with EtOAc. The combined organic phases were washed with water, then brine, dried over MgSO4, concentrated and purified with Combiflash (silica gel, 0-100% EtOAc/Hex) to give the desired product (0.145 g, 60%) as colorless oil. LCMS calculated for C23H33N6O3Si(M+H)+: 469.2; Found: 469.4.

Workup

  1. customThe mixture was partitioned between water and EtOAc
  2. customThe phases were separated
  3. washthe aq. phase was washed with EtOAc
  4. washThe combined organic phases were washed with water
  5. dry with materialbrine, dried over MgSO4
  6. concentrationconcentrated
  7. custompurified with Combiflash (silica gel, 0-100% EtOAc/Hex)

Sources & evidence

ORD record
ord-630a980b2a204cae89d4e49f2d073496
Source dataset
uspto-grants-2012_04
Patent number
US08158616B2

Reaction notes

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