Trifluoroacetic acid → (+/-)-5-[3-Methyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carboxylic acid methyl ester

HRID 2173851Notes

Reaction equation

HRID 2173851 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:10]=[CH:9][C:8]([N:11](C(OC(C)(C)C)=O)[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].FC(F)(F)C(O)=O>ClCCl>[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]([NH:11][CH:12]([C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:24]=[CH:25][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:27][CH:28]=3)=[CH:19][CH:18]=2)[CH2:13][CH:14]([CH3:16])[CH3:15])=[CH:9][N:10]=1)=[O:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 68062019(+/-)-5-{Tert-butoxycarbonyl-[3-methyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-butyl]-amino}-pyrimidine-2-carboxylic acid methyl ester

Product 1

HCID 67983778(+/-)-5-[3-Methyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carboxylic acid methyl esterYield 50.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(+/−)-5-{tert-Butoxycarbonyl-[3-methyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-butyl]-amino}-pyrimidine-2-carboxylic acid methyl ester (1.498 g impure) was dissolved in dichloromethane (10 mL) and trifluoroacetic acid (3 mL) was added. This was stirred at room temperature. At 70 min, another 3 mL of trifluoroacetic acid was added. At 90 min, the reaction was concentrated and the material was partitioned between ethyl acetate and sat. NaHCO3. The aqueous layer was extracted with ethyl acetate and the combined organics dried over MgSO4. Purification by silica gel flash chromatography (ethyl acetate/heptane) gave (+/−)-5-[3-methyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carboxylic acid methyl ester (0.620 g) as a white foam. 1H NMR (400 MHz, CDCl3, δ): 8.16 (s, 2H) 7.67-7.73 (m, 2H) 7.61-7.66 (m, 2H) 7.56 (d, J=8.2 Hz, 2H) 7.39 (d, J=8.2 Hz, 2H) 4.68 (d, J=5.7 Hz, 1H) 4.46-4.57 (m, 1H) 3.98 (s, 3H) 1.79-1.92 (m, 1H) 1.64-1.79 (m, 2H) 1.05 (d, J=6.2 Hz, 3H) 0.99 (d, J=6.2 Hz, 3H); MS (M+1): 444.3.

Workup

  1. waitAt 90 min
  2. concentrationthe reaction was concentrated
  3. customthe material was partitioned between ethyl acetate and sat. NaHCO3
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organics dried over MgSO4
  6. customPurification by silica gel flash chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-0570daac0bfe4877a2a4eda8681be87c
Source dataset
uspto-grants-2015_06
Patent number
US09056834B2

Reaction notes

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