4-(Trifluoromethyl)benzoyl chloride → HCID 59514495, compound

HRID 537019Notes

Reaction equation

HRID 537019 reaction equation
[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[C:6]([N:22]([CH3:24])[CH3:23])=[N:7][C:8]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=2)=[N:9][C:10]=1[N:11]([CH3:13])[CH3:12].C(N(C(C)C)CC)(C)C.[F:35][C:36]([F:47])([F:46])[C:37]1[CH:45]=[CH:44][C:40]([C:41](Cl)=[O:42])=[CH:39][CH:38]=1>CO>[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[C:6]([N:22]([CH3:23])[CH3:24])=[N:7][C:8]([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([NH:21][C:41](=[O:42])[C:40]3[CH:44]=[CH:45][C:37]([C:36]([F:35])([F:46])[F:47])=[CH:38][CH:39]=3)=[CH:19][CH:20]=2)=[N:9][C:10]=1[N:11]([CH3:12])[CH3:13]

Participants

5

Reactant 3

HCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 81531DiisopropylethylamineHCID 59514565HCID 59514565, compound

Product 1

HCID 59514495HCID 59514495, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred suspension of [4,6-bis-dimethylamino-2-(4-aminobenzyl)pyrimidin-5-yl]acetic acid methyl ester (100 g, obtained according to step C) in 700 mL of methanol in a 1500 mL double jacketed vessel at 20±5° C. is added diisopropylethylamin (41.4 g) over a period of 30 minutes while heating the reaction mixture to 50±5° C. 4-Trifluoromethylbenzoic acid chloride (63.8 g) is added during further 30 minutes. The reaction mixture is stirred for 15 minutes at 50±5° C. and subsequently heated to 65±5° C. (reflux conditions) and stirred for another 30 minutes. The resulting suspension is gradually cooled to 5±5° C. over a period of 2 hours and stirred at this temperature for 1 hour. The solid is filtered off, washed with 200 mL of isopropanol and dried in vacuo at 50° C. to yield [4,6-bis-dimethylamino-2-[4-(4-trifluoromethylbenzoylamino)benzyl]pyrimidin-5-yl]acetic acid methyl ester in an amount of 135.8 g (yield: 90%; HPLC-purity: 99.5%).

Workup

  1. temperaturesubsequently heated to 65±5° C.
  2. temperature(reflux conditions)
  3. stirringstirred for another 30 minutes
  4. temperatureThe resulting suspension is gradually cooled to 5±5° C. over a period of 2 hours
  5. stirringstirred at this temperature for 1 hour
  6. filtrationThe solid is filtered off
  7. washwashed with 200 mL of isopropanol
  8. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-3a3a2718280a4b099f3f23e99477d919
Source dataset
uspto-grants-2014_10
Patent number
US08859770B2

Reaction notes

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