Sodium Hydroxide → HCID 11684638, compound

HRID 2110740Notes

Reaction equation

HRID 2110740 reaction equation
C[O:2][C:3](=[O:36])[C:4]([C:7]1[CH:12]=[C:11]([C:13]2[CH:18]=[C:17]([NH:19][CH2:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=3)[N:16]=[C:15]([O:33][CH3:34])[N:14]=2)[CH:10]=[CH:9][C:8]=1[F:35])([CH3:6])[CH3:5].[OH-].[Na+]>O.CO.C1COCC1>[F:35][C:8]1[CH:9]=[CH:10][C:11]([C:13]2[CH:18]=[C:17]([NH:19][CH2:20][CH2:21][C:22]3[CH:23]=[CH:24][C:25]([O:28][C:29]([F:32])([F:30])[F:31])=[CH:26][CH:27]=3)[N:16]=[C:15]([O:33][CH3:34])[N:14]=2)=[CH:12][C:7]=1[C:4]([CH3:6])([CH3:5])[C:3]([OH:36])=[O:2]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 69064866HCID 69064866, compound

Product 1

HCID 11684638HCID 11684638, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(2-fluoro-5-{2-methoxy-6-[2-(4-trifluoromethoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid methyl ester (should this be the right starting material? 1.9 g) and sodium hydroxide (2.46 g) in water (19 mL), MeOH (19 mL) and THF (19 mL) is stirred at 40° C. for 40 hours. The solution is evaporated in vacuo and acidified to pH=6 with concentrated HCl (1.6 mL). The solid is filtered, air dried and chromatographed on silica gel eluting with 50% EtOAc in heptane to afford 2-(2-fluoro-5-{2-methoxy-6-[2-(4-trifluoromethoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid (1.12 g, Example 70). MS: 494 (M+H); 1H NMR (300 MHz, CD3OD), □7.8, (d, 1H, J=0.3 Hz); 7.7 (m, 1H); 7.4 (d, 2H, J=0.4 Hz); 7.2-7.3 (m, 4H); 6.6 (s, 1H); 4.2 (s, 3H); 3.9 (m, 2H); 3.05 (t, 2H); 1.65 (s, 6H). IC50=193 nM

Workup

  1. customThe solution is evaporated in vacuo
  2. filtrationThe solid is filtered
  3. customair dried
  4. customchromatographed on silica gel eluting with 50% EtOAc in heptane

Sources & evidence

ORD record
ord-e19d2b85cb2043c581bf49b5fa1846bf
Source dataset
uspto-grants-2009_04
Patent number
US07517889B2

Reaction notes

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