Heptane → Sodium 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionate

HRID 216188Notes

Reaction equation

HRID 216188 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][NH:11][C:12]1[N:17]=[C:16]([O:18][CH3:19])[N:15]=[C:14]([C:20]2[CH:21]=[C:22]([C:26]([CH3:31])([CH3:30])[C:27]([OH:29])=[O:28])[CH:23]=[CH:24][CH:25]=2)[CH:13]=1.C([O-])([O-])=O.[Na+:36].[Na+].CCCCCCC>CO>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][NH:11][C:12]1[N:17]=[C:16]([O:18][CH3:19])[N:15]=[C:14]([C:20]2[CH:21]=[C:22]([C:26]([CH3:31])([CH3:30])[C:27]([O-:29])=[O:28])[CH:23]=[CH:24][CH:25]=2)[CH:13]=1.[Na+:36]

Participants

5

Reactant 3

HCID 8900HeptaneHCID 10340Sodium CarbonateHCID 11669780Pgd2-IN-1

Product 1

HCID 69063384Sodium 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid [540 mg, 1.17 mmol, Example 49(b)] in MeOH (60 mL) is treated with Na2CO3 (187 mg, 1.78 mmol) and the mixture is stirred for 15 hours. The reaction mixture is filtered and the filtrate is concentrated to dryness. To the residue is added a mixture of methanol, EtOAc and acetone. The insoluble material is filtered off and the filtrate is evaporated. The residue is again treated with a mixture of methanol, EtOAc and acetone, the insoluble material filtered off and the filtrate is evaporated. The residue is again treated with a mixture of methanol, EtOAc and acetone, the insoluble material filtered off and the filtrate is evaporated. To the residue is added MeOH (1 mL) and EtOAc (5 mL), followed by heptane until the solution turned cloudy and a solid is formed slowly. Heptane is repeatedly added until the solution stay clear. The mixture is filtered affording sodium 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionate as a crystalline. LC/MS: RT=2.34 minutes, MS: 460 (M-Na+ 2H)+. 1H NMR [300 MHz, (CD3)2SO]: □ 7.97 (1H, br s), 7.24-7.7 (7H, m), 6.57 (1H, s), 3.86 (3H, s), 3.58 (2H, m), 2.98 (2H, m), 1.4 (6H, s).

Workup

  1. filtrationThe reaction mixture is filtered
  2. concentrationthe filtrate is concentrated to dryness
  3. additionTo the residue is added
  4. additiona mixture of methanol, EtOAc and acetone
  5. filtrationThe insoluble material is filtered off
  6. customthe filtrate is evaporated
  7. additionThe residue is again treated with a mixture of methanol, EtOAc and acetone
  8. filtrationthe insoluble material filtered off
  9. customthe filtrate is evaporated
  10. additionThe residue is again treated with a mixture of methanol, EtOAc and acetone
  11. filtrationthe insoluble material filtered off
  12. customthe filtrate is evaporated
  13. additionTo the residue is added MeOH (1 mL) and EtOAc (5 mL)
  14. customa solid is formed slowly
  15. filtrationThe mixture is filtered

Sources & evidence

ORD record
ord-ef87e6bf598c42eca54e39b6d57ee532
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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