(1-Benzylpiperazin-2-yl)methanol → {(R)-2-[5-(4-benzyl-3-hydroxymethyl-piperazin-1-yl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethyl}-carbamic acid tert-butyl ester

HRID 574268Notes

Reaction equation

HRID 574268 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH:9]1[CH2:14][OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16]([O:20][C:21](=[O:53])[NH:22][C@H:23]([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[CH2:24][N:25]1[C:30](=[O:31])[C:29](Br)=[C:28]([CH3:33])[N:27]([CH2:34][C:35]2[C:40]([C:41]([F:44])([F:43])[F:42])=[CH:39][CH:38]=[CH:37][C:36]=2[F:45])[C:26]1=[O:46])([CH3:19])([CH3:18])[CH3:17]>C(#N)C>[C:16]([O:20][C:21](=[O:53])[NH:22][C@H:23]([C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1)[CH2:24][N:25]1[C:30](=[O:31])[C:29]([N:11]2[CH2:12][CH2:13][N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:9]([CH2:14][OH:15])[CH2:10]2)=[C:28]([CH3:33])[N:27]([CH2:34][C:35]2[C:40]([C:41]([F:44])([F:43])[F:42])=[CH:39][CH:38]=[CH:37][C:36]=2[F:45])[C:26]1=[O:46])([CH3:17])([CH3:18])[CH3:19]

Participants

4

Reactant 2

HCID 19763548(1-Benzylpiperazin-2-yl)methanolHCID 210184011,1-Dimethylethyl N-[(1R)-2-[5-bromo-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-3,6-dihydro-4-methyl-2,6-dioxo-1(2H)-pyrimidinyl]-1-phenylethyl]carbamate

Product 1

HCID 67143707{(R)-2-[5-(4-benzyl-3-hydroxymethyl-piperazin-1-yl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethyl}-carbamic acid tert-butyl esterYield 33.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

(1-Benzyl-piperazin-2-yl)-methanol (200 mg, 0.97 mmol), {(R)-2-[5-bromo-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethyl}-carbamic acid tert-butyl ester (50 mg, 0.083 mmol), and acetonitrile (1 mL) were placed in a microwave vessel and stirred at 120° C. for 3 hrs with microwave irradiation. After concentration of the solution, the residue was purified using silica gel chromatography (eluent: hexane/ethyl acetate/dichloromethane, 1/1/1) and dried in a vacuum to afford 20 mg of a colorless oil (yield 33%) . 1H NMR (300 MHz, CDCl3) δ 1.37 (9H, s), 2.23 (1H, m), 2.34 (3H, s), 2.41-2.66 (2H, m), 2.85 (1H, m), 3.16 (1H, m), 3.49 (1H, m), 3.72 (1H, m), 3.93-4.15 (3H, m), 4.21 (1H, m), 5.03 (1H, m), 5.42 (2H, dd), 5.74 (1H, m), 7.21 (2H, m), 7.18-7.26 (10H, m), 7.54 (1H, d)

Workup

  1. customAfter concentration of the solution, the residue was purified
  2. customdried in a vacuum

Sources & evidence

ORD record
ord-bfbfda9afa3b46c2b3f2781be120c942
Source dataset
uspto-grants-2015_05
Patent number
US09034850B2

Reaction notes

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