Dimethyl Sulfoxide → Tris(1,1-dimethylethyl) 2-{2-chloro-5-fluoro-6-[(4-methyl-1-piperazinyl)(1,3-thiazol-2-ylmethyl)amino]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate

HRID 1366704Notes

Reaction equation

HRID 1366704 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([NH:8][CH2:9][C:10]2[S:11][CH:12]=[CH:13][N:14]=2)[CH2:4][CH2:3]1.C(N(CC)CC)C.[CH3:22][C:23]([O:26][C:27]([N:29]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[N:30]([C:38]1[C:43]([F:44])=[C:42](Cl)[N:41]=[C:40]([Cl:46])[N:39]=1)[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=[O:28])([CH3:25])[CH3:24].CS(C)=O>C1COCC1>[Cl:46][C:40]1[N:39]=[C:38]([N:30]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[N:29]([C:27]([O:26][C:23]([CH3:22])([CH3:24])[CH3:25])=[O:28])[C:47]([O:49][C:50]([CH3:51])([CH3:52])[CH3:53])=[O:48])[C:43]([F:44])=[C:42]([N:8]([N:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]2)[CH2:9][C:10]2[S:11][CH:12]=[CH:13][N:14]=2)[N:41]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 58000755Tris(1,1-dimethylethyl) 2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylateHCID 669362614-methyl-N-(1,3-thiazol-2-ylmethyl)-1-piperazinamine

Product 1

HCID 86637031Tris(1,1-dimethylethyl) 2-{2-chloro-5-fluoro-6-[(4-methyl-1-piperazinyl)(1,3-thiazol-2-ylmethyl)amino]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylateYield 3.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Methyl-N-(1,3-thiazol-2-ylmethyl)-1-piperazinamine (2.2169 g, 10.44 mmol) was dissolved in THF (30 mL) and triethylamine (4.37 ml, 31.3 mmol). Then tris(1,1-dimethylethyl)2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate (3.89 g, 7.83 mmol) and DMSO (5 mL) were added. The reaction was left to stir overnight. The THF was evaporated away, and the mixture was diluted with water. The aqueous layer was extracted with ethyl acetate, and the organics were dried (Na2SO4) and evaporated. Purification by silica gel chromatography and RP-HPLC provided tris(1,1-dimethylethyl) 2-{2-chloro-5-fluoro-6-[(4-methyl-1-piperazinyl)(1,3-thiazol-2-ylmethyl)amino]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate (0.2014 g, 3%). LCMS: (M+H)+=674.6.

Workup

  1. waitThe reaction was left
  2. customThe THF was evaporated away
  3. additionthe mixture was diluted with water
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe organics were dried (Na2SO4)
  6. customevaporated
  7. customPurification by silica gel chromatography and RP-HPLC

Sources & evidence

ORD record
ord-d90ce5035a1240ab9d99903903f8e990
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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