4,6-Dichloro-pyrimidine-5-carbonyl chloride → methyl 2-(4-(4-(N-(2-(tert-butyldimethylsilyloxy) ethyl)-4,6-dichloropyrimidine-5-carboxamido)-3-fluorophenyl)cyclohexyl)acetate

HRID 2237622Notes

Reaction equation

HRID 2237622 reaction equation
[Cl:1][C:2]1[C:7]([C:8](Cl)=[O:9])=[C:6]([Cl:11])[N:5]=[CH:4][N:3]=1.[Si:12]([O:19][CH2:20][CH2:21][NH:22][C:23]1[CH:28]=[CH:27][C:26]([CH:29]2[CH2:34][CH2:33][CH:32]([CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH2:31][CH2:30]2)=[CH:25][C:24]=1[F:40])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]>C1COCC1>[Si:12]([O:19][CH2:20][CH2:21][N:22]([C:23]1[CH:28]=[CH:27][C:26]([CH:29]2[CH2:34][CH2:33][CH:32]([CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH2:31][CH2:30]2)=[CH:25][C:24]=1[F:40])[C:8]([C:7]1[C:6]([Cl:11])=[N:5][CH:4]=[N:3][C:2]=1[Cl:1])=[O:9])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]

Participants

4

Reactant 2

HCID 121633604,6-Dichloro-pyrimidine-5-carbonyl chlorideHCID 59302498HCID 59302498, compound

Product 1

HCID 59302507methyl 2-(4-(4-(N-(2-(tert-butyldimethylsilyloxy) ethyl)-4,6-dichloropyrimidine-5-carboxamido)-3-fluorophenyl)cyclohexyl)acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4,6-dichloropyrimidine-5-carbonyl chloride (82.5 mg, 0.390), methyl 2-(4-(4-(2-(tert-butyldimethylsilyloxy)ethylamino)-3-fluorophenyl)cyclohexyl)acetate (110 mg, 0.26 mmol) and TEA (0.054 mL, 0.39 mmol) in THF (2 mL) was stirred at room temperature under nitrogen for 14 hours. The reaction mixture was concentrated to remove THF. The residue was diluted with EtOAc, washed with water, dried over MgSO4 and concentrated. The crude material was purified by a 12 g silica gel column eluted with 3-15% EtOAc in heptane to give methyl 2-(4-(4-(N-(2-(tert-butyldimethylsilyloxy) ethyl)-4,6-dichloropyrimidine-5-carboxamido)-3-fluorophenyl)cyclohexyl)acetate a colorless oil (60 mg). m/z=598.2 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto remove THF
  3. additionThe residue was diluted with EtOAc
  4. washwashed with water
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe crude material was purified by a 12 g silica gel column
  8. washeluted with 3-15% EtOAc in heptane

Sources & evidence

ORD record
ord-973ea8da1c4f4e66839b858e6c877a31
Source dataset
uspto-grants-2010_05
Patent number
US07718645B2

Reaction notes

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