Isopropylamine → Tris(1,1-dimethylethyl) 2-{2-chloro-5-fluoro-6-[(1-methylethyl)amino]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate

HRID 1366396Notes

Reaction equation

HRID 1366396 reaction equation
[CH:1]([NH2:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[CH3:14][C:15]([O:18][C:19]([N:21]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[N:22]([C:30]1[C:35]([F:36])=[C:34](Cl)[N:33]=[C:32]([Cl:38])[N:31]=1)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:20])([CH3:17])[CH3:16]>CN(C=O)C.C(OCC)C>[CH3:17][C:15]([O:18][C:19]([N:21]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[N:22]([C:30]1[C:35]([F:36])=[C:34]([NH:4][CH:1]([CH3:3])[CH3:2])[N:33]=[C:32]([Cl:38])[N:31]=1)[C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])=[O:20])([CH3:14])[CH3:16]

Participants

6

Reactant 3

HCID 6363IsopropylamineHCID 81531DiisopropylethylamineHCID 58000755Tris(1,1-dimethylethyl) 2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate

Product 1

HCID 86636921Tris(1,1-dimethylethyl) 2-{2-chloro-5-fluoro-6-[(1-methylethyl)amino]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylateYield 95%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a vigorously stirred solution of isopropyl amine (83 μL, 1.21 mmol) in DMF (6 mL) at 0° C. was added DIPEA (0.24 mL, 1.33 mmol) followed immediately by tris(1,1-dimethylethyl)2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate (600 mg, 1.21 mmol). When the reaction was complete as determined by LCMS, the reaction mixture was diluted with diethyl ether (˜40 mL) and washed with water (3×40 mL). The combined three aqueous layers were back-extracted once with diethyl ether, and then the combined organics were dried (Na2SO4) and concentrated in vacuo. This crude product was purified by flash chromatography (Combiflash, 5-60% ethyl acetate/hexanes, 1% triethylamine) to provide tris(1,1-dimethylethyl)2-{2-chloro-5-fluoro-6-[(1-methylethyl)amino]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate (597 mg, 95%). LCMS: (M+H)+: 520.2.

Workup

  1. washwashed with water (3×40 mL)
  2. extractionwere back-extracted once with diethyl ether
  3. dry with materialthe combined organics were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThis crude product was purified by flash chromatography (Combiflash, 5-60% ethyl acetate/hexanes, 1% triethylamine)

Sources & evidence

ORD record
ord-c5666b84c0874309a8b3d9e90102fbb2
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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