Triethylamine → N-(cyanomethyl)-4-methyl-2-(2-phenyl-1,3-thiazol-4-yl)pentanamide

HRID 1060748Notes

Reaction equation

HRID 1060748 reaction equation
[CH3:1][CH:2]([CH3:19])[CH2:3][CH:4]([C:8]1[N:9]=[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[S:11][CH:12]=1)[C:5]([OH:7])=O.C1CN([P+](O[N:37]2N=[N:44][C:39]3C=CC=C[C:38]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.NCC#N.C(N(CC)CC)C>CN(C=O)C>[C:38]([CH2:39][NH:44][C:5](=[O:7])[CH:4]([C:8]1[N:9]=[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[S:11][CH:12]=1)[CH2:3][CH:2]([CH3:1])[CH3:19])#[N:37]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 110766664-Methyl-2-(2-phenylthiazol-4-yl)pentanoic acidHCID 11491918Aminoacetonitrile hydrochloride

Product 1

HCID 11034349N-(cyanomethyl)-4-methyl-2-(2-phenyl-1,3-thiazol-4-yl)pentanamideYield 76.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution comprised of 4-methyl-2-(2-phenylthiazol-4-yl)pentanoic acid (150 mg, 0.6 mmol), prepared as in Example 5, in DMF (5.0 mL) was treated with PyBOP (300 mg, 0.7 mmol), aminoacetonitrile hydrochloride (100 mg, 1 mmol) and triethylamine (250 μL, 1.5 mmol). The mixture was stirred for 3 hours and then partitioned between water (20 mL) and ethyl acetate (50 mL). The organic layer was separated and washed with 1 M saturated sodium bicarbonate solution, 1 M hydrochloric acid solution and water, dried (MgSO4) and concentrated. Product was purified from the residue by flash column on silica gel (60° A) with 40% ethyl acetate in hexane to provide N-cyanomethyl-4-methyl-2-(2-phenylthiazol-4-yl)pentanamide (120 mg, 0.46 mmol). Rf 0.30. 1H NMR (DMSO-d6): 1.01 (m, 6H), 1.31-1.59 (m, 3H), 3.91 (m, 1H), 4.14 (s, 2H), 7.44 (m, 4H), 7.81 (m, 2H), 8.61 (s, 1H). LCMS: 312.2.0 (M+H+).

Workup

  1. custompartitioned between water (20 mL) and ethyl acetate (50 mL)
  2. customThe organic layer was separated
  3. washwashed with 1 M saturated sodium bicarbonate solution, 1 M hydrochloric acid solution and water
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customProduct was purified from the residue by flash column on silica gel (60° A) with 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-46f722cd0e034a9ca2ca4bb62b811de3
Source dataset
uspto-grants-2003_02
Patent number
US06525036B2

Reaction notes

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