Sodium hydride → Methyl (2E)-4-{[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino}-4-methylpent-2-enoate

HRID 1436430Notes

Reaction equation

HRID 1436430 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([CH2:7]P(OC)(OC)=O)=[O:6].[CH3:14][C:15]([NH:19][C:20]1[S:21][CH:22]=[C:23]([C:25]2[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=2)[N:24]=1)([CH3:18])[CH:16]=O>O1CCCC1>[C:29]([C:28]1[CH:27]=[CH:26][C:25]([C:23]2[N:24]=[C:20]([NH:19][C:15]([CH3:18])([CH3:16])/[CH:14]=[CH:7]/[C:5]([O:4][CH3:3])=[O:6])[S:21][CH:22]=2)=[CH:32][CH:31]=1)#[N:30]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 866186094-{2-[(1,1-Dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile

Product 1

HCID 86618612Methyl (2E)-4-{[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino}-4-methylpent-2-enoateYield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (60% in oil, 0.17 g, 4.5 mmol) in tetrahydrofuran (30 mL) was added trimethyl phosphonoacetate (0.75 mL, 5.2 mmol) dropwise and the mixture was stirred for 45 min. A solution of 4-{2-[(1,1-dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile (0.81 g, 3.0 mmol), prepared in step 1 of Example 83, in 5 mL of tetrahydrofuran was added and the mixture was stirred at 25° C. for 2 h. The reaction was quenched with saturated NH4Cl and diluted with ethyl acetate and washed with H2O, brine, dried over anhydrous MgSO4, filtered and concentrated. Flash chromatography (20% acetone/hexane) afforded methyl (2E)-4-{[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino}-4-methylpent-2-enoate (0.91 g, 93%) as a white solid. HRMS: calcd for C17H17N3O2S+H+, 328.11142; found (ESI, [M+H]+), 328.1135; Analytical HPLC: purity 100% at 210-370 nm, 9.9 min; 100% at 252 nm, 9.9 min; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammon. Form. Buff. pH=3.5/ACN+MeOH) for 10 min, hold 4 min.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at 25° C. for 2 h
  3. customThe reaction was quenched with saturated NH4Cl
  4. additiondiluted with ethyl acetate
  5. washwashed with H2O, brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-93e9fec51a464378b144764fd9ee8bf8
Source dataset
uspto-grants-2009_11
Patent number
US07618990B2

Reaction notes

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