Trifluoroacetic acid → 1-(2,5-Dichloro-pyrimidin-4-yl)-piperidine-4-carboxylic acid [1-(3-chloro-phenyl)-2-hydroxy-ethyl]-amide

HRID 1295675Notes

Reaction equation

HRID 1295675 reaction equation
C(OC(N1CCN([C:14](=[O:26])[NH:15][CH:16]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=2)[CH2:17][OH:18])CC1)=O)(C)(C)C.F[C:28](F)(F)[C:29](O)=O.[Cl:34][C:35]1[N:40]=[C:39](Cl)[C:38]([Cl:42])=[CH:37][N:36]=1>C(Cl)Cl>[Cl:25][C:21]1[CH:20]=[C:19]([CH:16]([NH:15][C:14]([CH:29]2[CH2:28][CH2:14][N:15]([C:39]3[C:38]([Cl:42])=[CH:37][N:36]=[C:35]([Cl:34])[N:40]=3)[CH2:16][CH2:17]2)=[O:26])[CH2:17][OH:18])[CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 2372592,4,5-TrichloropyrimidineHCID 694145564-[1-(3-Chloro-phenyl)-2-hydroxy-ethylcarbamoyl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 866013611-(2,5-Dichloro-pyrimidin-4-yl)-piperidine-4-carboxylic acid [1-(3-chloro-phenyl)-2-hydroxy-ethyl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-[1 -(3-Chloro-phenyl)-2-hydroxy-ethylcarbamoyl]-piperazine- 1-carboxylic acid tert-butyl ester was deprotected with 10% trifluoroacetic acid in methylene chloride by stirring overnight at ambient temperature. The reaction was concentrated in vacuo and the resulting TFA salt was dissolved in DMF (1 mL) and DIEA (0.25 mL). This mixture was heated with 2,4,5-trichloropyrimidine (52 mg. 0.28 mmol) at 80° C. for 18 hours. Purification by prep HPLC (Gilson: Column=CombiHT SB-C189 5 μM 21.2 mm×100 mm, eluent=0.1% TFA MeCN/H2O gradient) afforded the title compound as a yellow oil (47 mg) Rt=5.97 minutes; MS FIA 429.9 (M+1).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe resulting TFA salt was dissolved in DMF (1 mL)
  3. customPurification by prep HPLC (Gilson: Column=CombiHT SB-C189 5 μM 21.2 mm×100 mm, eluent=0.1% TFA MeCN/H2O gradient)

Sources & evidence

ORD record
ord-0cd86aae0bcc488387d5491d8850ab71
Source dataset
uspto-grants-2007_07
Patent number
US07244735B2

Reaction notes

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