Sodium hydride → 2-(6-(4-Acetylpiperazin-1-yl)pyrimidin-4-ylamino)thiazole-5-carbonitrile

HRID 1241390Notes

Reaction equation

HRID 1241390 reaction equation
OC(C(F)(F)F)=O.[NH2:8][C:9]1[N:14]=[CH:13][N:12]=[C:11]([N:15]2[CH2:20][CH2:19][N:18]([C:21](=[O:23])[CH3:22])[CH2:17][CH2:16]2)[CH:10]=1.[H-].[Na+].Cl[C:27]1[S:28][C:29]([C:32]#[N:33])=[CH:30][N:31]=1>C1COCC1.O>[C:21]([N:18]1[CH2:19][CH2:20][N:15]([C:11]2[N:12]=[CH:13][N:14]=[C:9]([NH:8][C:27]3[S:28][C:29]([C:32]#[N:33])=[CH:30][N:31]=3)[CH:10]=2)[CH2:16][CH2:17]1)(=[O:23])[CH3:22]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 14852222-Chlorothiazole-5-carbonitrile2×HCID 865859561-[4-(6-Amino-pyrimidin-4-yl)-piperazin-1-yl]-ethanone TFA salt

Product 1

HCID 219346372-(6-(4-Acetylpiperazin-1-yl)pyrimidin-4-ylamino)thiazole-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-[4-(6-Amino-pyrimidin-4-yl)-piperazin-1-yl]-ethanone TFA salt (72 mg, 0.22 mmol) was stirred in anhydrous THF under N2. Sodium hydride (26 mg, 60% dispersion, 0.65 mmol) was added followed by the addition of 2-chlorothiazole-5-carbonitrile (62 mg, 0.43 mmol). The reaction was heated to reflux and after 30 minutes additional 2-chloro-thiazole-5-carbonitrile (85 mg, 0.59 mmol) was added. After a total of 1.5 hours, the reaction was cooled to room temperature, diluted with water and the bulk of the tHF was removed in vacuo. The resulting mixture was adjusted to pH 7 with 1 M HCl (aq). The resulting precipitate was filtered, washed with water and after air drying was washed with hexane. 1H-NMR (400 MHz, DMSO) 12.11 (1H, s), 8.45 (1H, s), 8.26 (1H, s), 6.23 (1H, s), 3.62–3.55 (m, 8H), 2.05 (s, 3H). M+1=330.2.

Workup

  1. temperatureThe reaction was heated
  2. additionwas added
  3. customthe bulk of the tHF was removed in vacuo
  4. filtrationThe resulting precipitate was filtered
  5. washwashed with water
  6. customafter air drying
  7. washwas washed with hexane

Sources & evidence

ORD record
ord-9d44af7b1e7f4890a008bc5bf544f147
Source dataset
uspto-grants-2006_10
Patent number
US07115597B2

Reaction notes

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