3,3-Dimethylbutanoyl chloride → n-[4-Amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-3,3-dimethylbutyramide

HRID 2245225Notes

Reaction equation

HRID 2245225 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[N:5]=[C:4]([NH2:20])[C:3]=1[NH2:21].[C:22]([CH2:26][C:27](Cl)=[O:28])([CH3:25])([CH3:24])[CH3:23]>C(#N)C>[NH2:20][C:4]1[C:3]([NH:21][C:27](=[O:28])[CH2:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[C:2]([CH3:1])[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]([F:18])([F:19])[F:17])=[CH:14][CH:15]=2)[N:5]=1

Participants

4

Reactant 2

HCID 815143,3-Dimethylbutanoyl chlorideHCID 592160216-Methyl-N*2*-(4-trifluoromethylbenzyl)-pyrimidine-2,4,5-triamine

Product 1

HCID 16113873n-[4-Amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-3,3-dimethylbutyramideYield 33.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a cold stirred solution (ice/water bath) of 6-methyl-N*2*-(4-trifluoromethyl-benzyl)-pyrimidine-2,4,5-triamine (341 mg, 1.15 mmol) in acetonitril (7.5 ml), tert-butylacetyl chloride (0.16 ml, 1.15 mmol) was added dropwise in 2 min. Cold bath was removed and stirring continued for 45 min. The obtained reaction mixture was poured into SCX column (10 g, H+ form), washed with acetonitrile (20 ml), methanol (100 ml), and the product was eluted with 4M NH3 in methanol (60 ml). The volatiles were removed in vacuo and the crude product was purified by flash chromatography on silica gel (20 g) with gradient heptane-ethyl acetate to give 153 mg of solid. Yield 33.7%. LC-MS (m/z) 395.9 (MH+); tR=2.00. 1H NMR (500 MHz, DMSO-d6): 1.02 (s, 9H), 1.96 (s, 3H), 2.15 (s, 2H), 4.5 (d, 2H), 5.9 (br, 2H, NH2), 6.97 (br, 1H, NH), 7.5 (d, 2H), 7.65 (d, 2H), 8.57 (s, 1H, NHCO).

Workup

  1. customCold bath was removed
  2. customThe obtained reaction mixture
  3. additionwas poured into SCX column (10 g, H+ form)
  4. washwashed with acetonitrile (20 ml), methanol (100 ml)
  5. washthe product was eluted with 4M NH3 in methanol (60 ml)
  6. customThe volatiles were removed in vacuo
  7. customthe crude product was purified by flash chromatography on silica gel (20 g) with gradient heptane-ethyl acetate

Sources & evidence

ORD record
ord-a374c6ed564545ca92d21e6d193033c7
Source dataset
uspto-grants-2010_03
Patent number
US07683058B2

Reaction notes

Loading…