Acetic Acid → [4,6-Bis(dimethylamino)-2-{4-[4-(trifluoromethyl)benzamido]benzyl}-5-pyrimidinyl]acetic acid

HRID 537020Notes

Reaction equation

HRID 537020 reaction equation
C[O:2][C:3](=[O:37])[CH2:4][C:5]1[C:6]([N:34]([CH3:36])[CH3:35])=[N:7][C:8]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:33])[C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[CH:17][CH:16]=2)=[N:9][C:10]=1[N:11]([CH3:13])[CH3:12].O.[OH-].[Li+].O.C(O)(=O)C>O1CCCC1.CO>[CH3:36][N:34]([CH3:35])[C:6]1[C:5]([CH2:4][C:3]([OH:37])=[O:2])=[C:10]([N:11]([CH3:12])[CH3:13])[N:9]=[C:8]([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([NH:21][C:22](=[O:33])[C:23]3[CH:24]=[CH:25][C:26]([C:29]([F:31])([F:32])[F:30])=[CH:27][CH:28]=3)=[CH:19][CH:20]=2)[N:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 59514495HCID 59514495, compound

Product 1

HCID 45270144[4,6-Bis(dimethylamino)-2-{4-[4-(trifluoromethyl)benzamido]benzyl}-5-pyrimidinyl]acetic acidYield 90%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A stirred suspension of [4,6-bis-dimethylamino-2-[4-(4-trifluoromethylbenzoylamino)-benzyl]pyrimidin-5-yl]acetic acid methyl ester (50 g, obtained according to step B) and lithium hydroxide monohydrate (6.3 g) in a mixture of 100 mL of tetrahydrofurane and 50 mL of methanol in a 1500 mL double jacketed vessel is heated to 60±5° C. over a period of 1 hour. Deionized water (75 mL) is slowly added. The obtained solution is stirred for 2 hours at 60±5° C. A solution of acetic acid (11.6 g) in 50 mL of methanol is added at 60±5° C. The resulting suspension is gradually cooled to 5±5° C. over a period of 2 hours and stirred at this temperature for another 30 minutes. The solid is filtered off, washed with 200 mL of methanol and dried in vacuo at 50° C. to yield [4,6-bis-dimethylamino-2-[4-(4-trifluoromethyl-benzoyl-amino)benzyl]pyrimidin-5-yl]acetic acid (compound of formula (I)) in an amount of 43.65 g (yield: 90%; HPLC-purity: 99.6%).

Workup

  1. temperatureThe resulting suspension is gradually cooled to 5±5° C. over a period of 2 hours
  2. stirringstirred at this temperature for another 30 minutes
  3. filtrationThe solid is filtered off
  4. washwashed with 200 mL of methanol
  5. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-53ad950b43a94807899733822ff4a14d
Source dataset
uspto-grants-2014_10
Patent number
US08859770B2

Reaction notes

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