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

HRID 1295676Notes

Reaction equation

HRID 1295676 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([NH:11][C:12]([CH:14]2[CH2:19][CH2:18][N:17]([C:20]3[C:25]([Cl:26])=[CH:24][N:23]=[C:22](Cl)[N:21]=3)[CH2:16][CH2:15]2)=[O:13])[CH2:9][OH:10])[CH:5]=[CH:6][CH:7]=1>C(O)C.C(N)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([NH:11][C:12]([CH:14]2[CH2:15][CH2:16][N:17]([C:20]3[C:25]([Cl:26])=[CH:24][N:23]=[C:22]([NH:11][CH:8]([CH3:9])[CH3:4])[N:21]=3)[CH2:18][CH2:19]2)=[O:13])[CH2:9][OH:10])[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 1

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

Product 1

HCID 866013621-(5-Chloro-2-isopropylamino-pyrimidin-4-yl)-piperidine-4-carboxylic acid [1-(3-chloro-phenyl)-2-hydroxy-ethyl]-amideYield 61.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6363IsopropylamineSolvent

Procedure

The 1-(2,5-dichloro-pyrimidin-4-yl)-piperidine-4-carboxylic acid [1-(3-chloro-phenyl)-2-hydroxy-ethyl]-amide (60 mg, 0.14 mmol) compound was dissolved in absolute ethanol (1 mL) and isopropyl amine (0.2 mL). The mixture was heated in a sealed Teflon reaction vial at 70° C. overnight. The resulting mixture was filtered and purified by preparative HPLC (Gilson: Column=CombiHT SB-C189 5 μM 21.2 mm×100 mm, eluent=0.1% TFA MeCN/H2O gradient). Further purification by preparative TLC (1 mm silica; eluent ethyl acetate) afforded the title compound as a colorless oil (19.5 mg) Rt=4.82 minutes; LCMS 453.1 (M+1); 1H NMR δ 7.87 (s, 1H) 7.25 (m, 4H) 5.28 (NH) 4.95 (dd, J=5.9, 3.9 Hz, 1H) 4.81 (NH) 4.01 (m, 1H) 3.89 (dd, J=11.2, 3.9 Hz, 1H) 3.83 (dd, J=11.2, 5.9 Hz, 1H) 3.65 (m, 4H) 3.52 (m 4H) 2.1 (OH) 1.20 (d, J=6.5 Hz, 6H).

Workup

  1. filtrationThe resulting mixture was filtered
  2. custompurified by preparative HPLC (Gilson: Column=CombiHT SB-C189 5 μM 21.2 mm×100 mm, eluent=0.1% TFA MeCN/H2O gradient)
  3. customFurther purification by preparative TLC (1 mm silica; eluent ethyl acetate)

Sources & evidence

ORD record
ord-4892867bcb6c4415854c46d8aaebf9de
Source dataset
uspto-grants-2007_07
Patent number
US07244735B2

Reaction notes

Loading…