4,6-Dichloro-pyrimidine-5-carbonyl chloride → HCID 178500655, compound

HRID 2237619Notes

Reaction equation

HRID 2237619 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.[CH3:12][O:13][C:14](=[O:40])[CH2:15][C@H:16]1[CH2:21][CH2:20][C@H:19]([C:22]2[CH:27]=[CH:26][C:25]([NH:28][CH2:29][C@H:30]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[CH3:31])=[CH:24][CH:23]=2)[CH2:18][CH2:17]1>C1COCC1>[CH3:12][O:13][C:14](=[O:40])[CH2:15][C@H:16]1[CH2:17][CH2:18][C@H:19]([C:22]2[CH:23]=[CH:24][C:25]([N:28]([CH2:29][C@H:30]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:34])[CH3:35])[CH3:31])[C:8]([C:7]3[C:6]([Cl:11])=[N:5][CH:4]=[N:3][C:2]=3[Cl:1])=[O:9])=[CH:26][CH:27]=2)[CH2:20][CH2:21]1

Participants

4

Reactant 2

HCID 121633604,6-Dichloro-pyrimidine-5-carbonyl chlorideHCID 178500654HCID 178500654, compound

Product 1

HCID 178500655HCID 178500655, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4,6-dichloropyrimidine-5-carbonyl chloride (2.27 g, 10.7 mmol), methyl[trans-4-(4-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}propyl]-amino}phenyl)cyclohexyl]acetate (4.50 g, 10.7 mmol), from Step 1, and TEA (2.24 mL, 16.1 mmol) in THF (150 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 (300 mL), washed with water (2×200 mL), dried over MgSO4 and concentrated. The crude material was purified by a 120 g silica gel column eluted with 3-15% EtOAc in heptane to give methyl[trans-4-(4-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}propyl][(4,6-dichloropyrimidin-5-yl)carbonyl]amino}phenyl)cyclohexyl]acetate as a colorless oil 4.01 g (63%). m/z=594.2 (M+1). 1H NMR (400 MHz, chloroform-d) δ −0.06 (s, 6H) 0.71 (s, 9H) 0.99-1.14 (m, 2H) 1.25-1.30 (m, 3H) 1.30-1.42 (m, 2H) 1.78 (dd, J=28.30, 11.90 Hz, 5H) 2.20 (d, J=7.03 Hz, 2H) 2.28-2.39 (m, 1H) 3.64 (s, 3H) 3.83-3.97 (m, 2H) 4.04-4.14 (m, 1H) 7.00 (d, J=8.20 Hz, 2H) 7.19 (d, J=8.59 Hz, 2H) 8.53 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto remove THF
  3. additionThe residue was diluted with EtOAc (300 mL)
  4. washwashed with water (2×200 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe crude material was purified by a 120 g silica gel column
  8. washeluted with 3-15% EtOAc in heptane

Sources & evidence

ORD record
ord-d222713236f24c2db2be3350725f44a1
Source dataset
uspto-grants-2010_05
Patent number
US07718645B2

Reaction notes

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