Hydrochloric Acid → 3-({5-[3-Methyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carbonyl}-amino)-propionic acid

HRID 1427499Notes

Reaction equation

HRID 1427499 reaction equation
C([O:3][C:4](=[O:38])[CH2:5][CH2:6][NH:7][C:8]([C:10]1[N:15]=[CH:14][C:13]([NH:16][CH:17]([C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=3)=[CH:24][CH:23]=2)[CH2:18][CH:19]([CH3:21])[CH3:20])=[CH:12][N:11]=1)=[O:9])C.FC(F)(F)C1C=CC(C2N=CC(NC(C3C=CC(C(NCCC(O)=O)=O)=CC=3)CCC)=CN=2)=CC=1.[OH-].[Na+].Cl>O1CCCC1.CO>[CH3:20][CH:19]([CH3:21])[CH2:18][CH:17]([NH:16][C:13]1[CH:12]=[N:11][C:10]([C:8]([NH:7][CH2:6][CH2:5][C:4]([OH:38])=[O:3])=[O:9])=[N:15][CH:14]=1)[C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:29]=[CH:30][C:31]([C:34]([F:36])([F:35])[F:37])=[CH:32][CH:33]=2)=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 679806583-({5-[3-Methyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carbonyl}-amino)-propionic acid ethyl esterHCID 679808383-(4-(1-(2-(4-(Trifluoromethyl)phenyl)pyrimidin-5-ylamino)butyl)benzamido)propanoic acid

Product 1

HCID 573888553-({5-[3-Methyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carbonyl}-amino)-propionic acidYield 78%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-({5-[3-methyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carbonyl}-amino)-propionic acid ethyl ester Peak 2 (150 mg, 0.284 mmol) was dissolved in tetrahydrofuran (3 mL) and methanol (1 mL), and 1.0 M NaOH (1 mL) was added. This was stirred at room temperature for 10 min. The reaction brought to pH 4 with 1 N HCl. This was extracted twice with ethyl acetate. The combined organics were dried over MgSO4 and concentrated in vacuo to give an oil. The material was triturated with four portions of diethylether to give the opposite enantiomer of 3-({5-[3-methyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carbonyl}-amino)-propionic acid (111 mg, 78%) as a white solid. 1H NMR (400 MHz, DMSO-d6, δ): 12.21 (br. s., 1H) 8.39 (t, J=6.0 Hz, 1H) 8.16 (s, 2H) 7.83-7.91 (m, 2H) 7.75-7.81 (m, 2H) 7.70 (d, J=8.2 Hz, 2H) 7.54 (d, J=8.2 Hz, 2H) 7.27 (d, J=7.6 Hz, 1H) 4.61-4.72 (m, 1H) 3.36-3.45 (m, 2H) 2.44 (t, J=6.9 Hz, 2H) 1.74-1.85 (m, 1H) 1.62-1.72 (m, 1H) 1.50-1.61 (m, 1H) 0.98 (d, J=6.4 Hz, 3H) 0.92 (d, J=6.4 Hz, 3H); MS (M+1): 501.6.

Workup

  1. extractionThis was extracted twice with ethyl acetate
  2. dry with materialThe combined organics were dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customto give an oil
  5. customThe material was triturated with four portions of diethylether

Sources & evidence

ORD record
ord-e766f815b38f4ddead985f815cf7c5a9
Source dataset
uspto-grants-2015_01
Patent number
US08933104B2

Reaction notes

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