Sodium hydride → 2-[4-(4-Acetyl-piperazin-1-ylmethyl)-3-methyl-pyridin-2-ylamino]-thiazole-5-carbonitrile

HRID 1355462Notes

Reaction equation

HRID 1355462 reaction equation
[H-].[Na+].[NH2:3][C:4]1[C:9]([CH3:10])=[C:8]([CH2:11][N:12]2[CH2:17][CH2:16][N:15]([C:18](=[O:20])[CH3:19])[CH2:14][CH2:13]2)[CH:7]=[CH:6][N:5]=1.Cl[C:22]1[S:23][C:24]([C:27]#[N:28])=[CH:25][N:26]=1>C1COCC1>[C:18]([N:15]1[CH2:14][CH2:13][N:12]([CH2:11][C:8]2[CH:7]=[CH:6][N:5]=[C:4]([NH:3][C:22]3[S:23][C:24]([C:27]#[N:28])=[CH:25][N:26]=3)[C:9]=2[CH3:10])[CH2:17][CH2:16]1)(=[O:20])[CH3:19]

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 14852222-Chlorothiazole-5-carbonitrileHCID 185068801-[4-(2-Amino-3-methyl-pyridin-4-ylmethyl)-piperazin-1-yl]-ethanone

Product 1

HCID 185068072-[4-(4-Acetyl-piperazin-1-ylmethyl)-3-methyl-pyridin-2-ylamino]-thiazole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaH (60% dispersion, 14 mg, 0.35 mmol) was stirred in 1 mL anhydrous THF. 1-[4-(2-Amino-3-methyl-pyridin-4-ylmethyl)-piperazin-1-yl]-ethanone (0.039 g, 0.157 mmol) was added followed, after 10 min by the addition of 2-chloro-thiazole-5-carbonitrile (0.027 g, 0.19 mmol). The reaction was stirred at RT for 30 min then was heated to reflux. After 2 h an additional 0.010 g NaH (0.25 mmol) was added. After 1 h the reaction was cooled to RT and quenched with water. The pH was adjusted to 7 with 1M HCl and the mixture was extracted 3× with EtOAc. The combined organic phases were dried over Na2SO4, filtered and concentrated. The residue was purified by reverse phase HPLC to provide the pure titled compound. TFA salt: 1H NMR (CD3OD) δ8.37 (d, 1H, J=5.1 Hz), 8.08 (s, 1H), 7.19 (d, 1H, J=5.1 Hz), 4.45 (s, 2H), 3.81 (bs, 4H), 3.35 (s, 4H), 2.47 (s, 3H), 2.15 (s, 3H). MS [M+H]+=357.3.

Workup

  1. temperaturethen was heated to reflux
  2. temperatureAfter 1 h the reaction was cooled to RT
  3. customquenched with water
  4. extractionthe mixture was extracted 3× with EtOAc
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-3fd180cf5b374d15bcc1dd4edacb97eb
Source dataset
uspto-grants-2003_07
Patent number
US06586423B2

Reaction notes

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