Diethyl (cyanomethyl)phosphonate → HCID 57477975, compound

HRID 1501489Notes

Reaction equation

HRID 1501489 reaction equation
CC(C)([O-])C.[K+].[C:7]([CH2:9]P(=O)(OCC)OCC)#[N:8].[CH3:18][Si:19]([CH3:46])([CH3:45])[CH2:20][CH2:21][O:22][CH2:23][N:24]1[C:28]2[N:29]=[CH:30][N:31]=[C:32]([C:33]3[CH:34]=[N:35][N:36]([CH:38]4[CH2:43][CH2:42][C:41](=O)[CH2:40][CH2:39]4)[CH:37]=3)[C:27]=2[CH:26]=[CH:25]1>C1COCC1>[CH3:18][Si:19]([CH3:46])([CH3:45])[CH2:20][CH2:21][O:22][CH2:23][N:24]1[C:28]2[N:29]=[CH:30][N:31]=[C:32]([C:33]3[CH:34]=[N:35][N:36]([CH:38]4[CH2:43][CH2:42][C:41](=[CH:9][C:7]#[N:8])[CH2:40][CH2:39]4)[CH:37]=3)[C:27]=2[CH:26]=[CH:25]1

Participants

5

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 23665647Potassium tert-butoxideHCID 574779764-[4-(7-[2-(Trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclohexanone

Product 1

HCID 57477975HCID 57477975, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 1.0 M potassium tert-butoxide in THF (1.90 mL) at 0° C. was added a solution of diethyl cyanomethylphosphonate (321 μL, 0.00198 mol) in THF (4 mL) dropwise. The reaction was held for 10 min, then it was added to a solution of 4-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclohexanone (743 mg, 0.00180 mol) in THF (5 mL) stirring at 0° C. under a nitrogen atmosphere. The reaction was stirred 1.5 h at rt. LCMS analysis showed clean conversion to the desired product. To the reaction mixture was then added water and EtOAc. The phases were separated and the aqueous phase was extracted with EtOAc. The combined organic extract was washed with water, then sat'd NaCl, then dried over Na2SO4, and concentrated to dryness to yield 0.76 g of a white crystalline solid (TLC (EtOAc) Rf 0.33). The product was purified by automatic flash chromatography on silica gel. Used 40 g column; flow 40 mL/min; [A=hexane] [B=EtOAc]; A, 2 min; Gradient to B in 20 min. Rotary evaporation yielded 0.70 g of a white crystalline solid (89% yield). 1H NMR (CDCl3) δ 8.9 (s, 1H); 8.3 (s, 2H); 7.4 (d, 1H); 7.3 (s, 1H); 6.9 (d, 1H); 5.7 (s, 2H); 5.3 (s, 1H, olefin); 4.5 (m, 1H, NCH); 3.6 (m, 2H); 3.2 (m, 1H); 2.7 (m, 1H); 2.5 (m, 4H); 2.1 (m, 2H); 1.0 (m, 2H); −0.1 (s, 9H). MS(ES) 435 (M+1).

Workup

  1. stirringThe reaction was stirred 1.5 h at rt

Sources & evidence

ORD record
ord-34037bab551141fc83d3753faef4be06
Source dataset
uspto-grants-2015_12
Patent number
US09206187B2

Reaction notes

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