Diethyl Ether → Tris(1,1-dimethylethyl) 2-(2-chloro-5-fluoro-6-{[2-methyl-2-(4-morpholinyl)propyl]amino}-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate

HRID 1366541Notes

Reaction equation

HRID 1366541 reaction equation
[CH3:1][C:2]([N:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1)([CH3:5])[CH2:3][NH2:4].C(N(C(C)C)CC)(C)C.[CH3:21][C:22]([O:25][C:26]([N:28]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[N:29]([C:37]1[C:42]([F:43])=[C:41](Cl)[N:40]=[C:39]([Cl:45])[N:38]=1)[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:27])([CH3:24])[CH3:23].CCOCC>CN(C=O)C>[CH3:24][C:22]([O:25][C:26]([N:28]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[N:29]([C:37]1[C:42]([F:43])=[C:41]([NH:4][CH2:3][C:2]([CH3:1])([N:6]2[CH2:7][CH2:8][O:9][CH2:10][CH2:11]2)[CH3:5])[N:40]=[C:39]([Cl:45])[N:38]=1)[C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])=[O:27])([CH3:21])[CH3:23]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 19896412-Methyl-2-(morpholin-4-yl)propan-1-amineHCID 58000755Tris(1,1-dimethylethyl) 2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate

Product 1

HCID 86636980Tris(1,1-dimethylethyl) 2-(2-chloro-5-fluoro-6-{[2-methyl-2-(4-morpholinyl)propyl]amino}-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylateYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of commercially-available [2-methyl-2-(4-morpholinyl)propyl]amine (0.158 g, 1.00 mmol) in DMF (10 mL) under a nitrogen atmosphere at 0° C., was added diisopropylethylamine (0.19 mL, 1.1 mmol) followed immediately by tris(1,1-dimethylethyl)2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate (0.497 g, 1.00 mmol). The reaction was allowed to reach room temperature and was stirred overnight. Then ether was added, and the mixture was washed with water. The aqueous layer was back extracted with ether, and the combined organics were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (5-60% ethyl acetate in hexanes, 1% triethylamine) to provide tris(1,1-dimethylethyl)2-(2-chloro-5-fluoro-6-{[2-methyl-2-(4-morpholinyl)propyl]amino}-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate as a clear oil (0.578 g, 94%). LCMS: (M+H)+=619.4.

Workup

  1. customto reach room temperature
  2. washthe mixture was washed with water
  3. extractionThe aqueous layer was back extracted with ether
  4. dry with materialthe combined organics were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by silica gel chromatography (5-60% ethyl acetate in hexanes, 1% triethylamine)

Sources & evidence

ORD record
ord-1b721ca6525e4c81b8e6d94e48535ad9
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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