Hydrochloric Acid → (+/-)-5-[3-Methyl-1-(4'-trifluoromet hyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carboxylic acid

HRID 2173852Notes

Reaction equation

C[O:2][C:3]([C:5]1[N:10]=[CH:9][C:8]([NH:11][CH:12]([C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[CH:19][CH:18]=2)[CH2:13][CH:14]([CH3:16])[CH3:15])=[CH:7][N:6]=1)=[O:4].[OH-].[Na+].Cl>O1CCCC1.CO>[CH3:15][CH:14]([CH3:16])[CH2:13][CH:12]([NH:11][C:8]1[CH:7]=[N:6][C:5]([C:3]([OH:4])=[O:2])=[N:10][CH:9]=1)[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:24]=[CH:25][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:27][CH:28]=2)=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 50 °C

Procedure

(+/−)-5-[3-Methyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carboxylic acid methyl ester (617 mg, 1.39 mmol) was dissolved in tetrahydrofuran (6 mL) and methanol (2 mL), and 1.0 M NaOH (6 mL, 6 mmol) was added. This was stirred at 50° C. for 2.5 h before cooling and bringing to pH 3 with 1 N HCl. This was extracted three times with ethyl acetate. The combined organics were dried over MgSO4 and concentrated in vacuo to give (+/−)-5-[3-methyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carboxylic acid with ethyl acetate (0.636 g) as clear foam. 1H NMR (400 MHz, DMSO-d6, δ): 8.18 (s, 2H) 7.84-7.91 (m, 2H) 7.75-7.81 (m, 2H) 7.71 (d, J=8.2 Hz, 2H) 7.55 (d, J=8.2 Hz, 2H) 7.42 (d, J=7.8 Hz, 1H) 4.63-4.74 (m, 1H) 1.74-1.85 (m, 1H) 1.67 (dt, J=13.1, 6.5 Hz, 1H) 1.51-1.61 (m, 1H) 0.98 (d, J=6.4 Hz, 3H) 0.93 (d, J=6.4 Hz, 3H); MS (M+1): 430.3.

Workup

temperaturebefore cooling
extractionThis was extracted three times with ethyl acetate
dry with materialThe combined organics were dried over MgSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-f9c9d5ec699d4f94ab8ea9b0cb2ecbf4
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09056834B2

Reaction notes

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