Diethyl (cyanomethyl)phosphonate → HCID 178437655, compound

HRID 1874940Notes

Reaction equation

HRID 1874940 reaction equation
C(OP([CH2:9][C:10]#[N:11])(OCC)=O)C.CC(C)([O-])C.[K+].[Cl:18][C:19]1[N:20]=[C:21]([CH2:46][CH3:47])[NH:22][C:23]=1[C:24]([NH:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([O:35][C:36]2[CH:41]=[C:40]([CH:42]=O)[CH:39]=[C:38]([Cl:44])[CH:37]=2)[C:29]=1[F:45])=[O:25]>C1COCC1>[Cl:18][C:19]1[N:20]=[C:21]([CH2:46][CH3:47])[NH:22][C:23]=1[C:24]([NH:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([O:35][C:36]2[CH:41]=[C:40](/[CH:42]=[CH:9]/[C:10]#[N:11])[CH:39]=[C:38]([Cl:44])[CH:37]=2)[C:29]=1[F:45])=[O:25]

Participants

5

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 23665647Potassium tert-butoxideHCID 178437658HCID 178437658, compound

Product 1

HCID 178437655HCID 178437655, compoundYield 76.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

A solution of diethylphosphonoacetonitrile (15 μL, 0.094 mmol) in THF (1 mL) was cooled to 5° C. in an ice bath and potassium t-butoxide (1 M in THF, 94 μL, 0.094 mmol) was added dropwise. The reaction was stirred at 5° C. for 30 min and a solution of 4-chloro-N-({4-chloro-3-[(3-chloro-5-formylphenyl)oxy]-2-fluorophenyl}methyl)-2-ethyl-1H-imidazole-5-carboxamide (40 mg, 0.085 mmol) in THF (1 mL) was added dropwise. The reaction was stirred at 5° C. for 30 min, warmed to room temperature and stirred for an additional 60 min. The reaction was quenched with water (1 mL) and concentrated to a yellow oil. The crude material was purified by column chromatography (10% to 100% EtOAc/hexanes gradient) to afford the title compound (32 mg, 76%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 12.69 (s, 1H), 8.05 (t, 1H), 7.58 (d, 1H), 7.53 (s, 1H), 7.47-7.44 (m, 1H), 7.31 (t, 1H), 7.23 (s, 1H), 7.00 (s, 1H), 6.58 (d, 1H), 4.49 (d, 2H), 2.55 (q, 2H), 1.13 (t, 3H). MS: m/z 493, 495 (M+1).

Workup

  1. stirringThe reaction was stirred at 5° C. for 30 min
  2. temperaturewarmed to room temperature
  3. stirringstirred for an additional 60 min
  4. customThe reaction was quenched with water (1 mL)
  5. concentrationconcentrated to a yellow oil
  6. customThe crude material was purified by column chromatography (10% to 100% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-4a2ec8c84139496cbfd4141fbf06a440
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

Loading…