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

HRID 1366672Notes

Reaction equation

HRID 1366672 reaction equation
[S:1]1[CH:5]=[C:4]([CH2:6][NH2:7])[N:3]=[CH:2]1.[CH3:8][C:9]([O:12][C:13]([N:15]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[N:16]([C:24]1[C:29]([F:30])=[C:28](Cl)[N:27]=[C:26]([Cl:32])[N:25]=1)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:14])([CH3:11])[CH3:10].C(N(CC)CC)C>C1COCC1.O>[CH3:11][C:9]([O:12][C:13]([N:15]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[N:16]([C:24]1[C:29]([F:30])=[C:28]([NH:7][CH2:6][C:4]2[N:3]=[CH:2][S:1][CH:5]=2)[N:27]=[C:26]([Cl:32])[N:25]=1)[C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])=[O:14])([CH3:8])[CH3:10]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 150636521,3-Thiazol-4-ylmethanamineHCID 58000755Tris(1,1-dimethylethyl) 2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate

Product 1

HCID 86637026Tris(1,1-dimethylethyl) 2-{2-chloro-5-fluoro-6-[(1,3-thiazol-4-ylmethyl)amino]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylateYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of (1,3-thiazol-4-ylmethyl)amine (0.1491 g, 1.308 mmol) in THF (10 mL) was added a solution of tris(1,1-dimethylethyl)2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate (0.649 g, 1.308 mmol) and triethylamine (0.22 mL, 1.5784 mmol) in THF (2 mL). Additional THF (3 mL) was added, and the reaction was stirred overnight. Then the reaction mixture was diluted with water, and the aqueous layer was extracted with ethyl acetate. The organics were dried (Na2SO4) and concentrated. The resulting crude material was purified by silica gel chromatography (0-100% ethyl acetate in hexanes) to produce tris(1,1-dimethylethyl)2-{2-chloro-5-fluoro-6-[(1,3-thiazol-4-ylmethyl)amino]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate as a yellow oil (0.51 g, 68%). LCMS: (M-2Boc)=375.0.

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate
  2. dry with materialThe organics were dried (Na2SO4)
  3. concentrationconcentrated
  4. customThe resulting crude material was purified by silica gel chromatography (0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5d8d4b4ffacf474db23e61dc851c9a93
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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