Trifluoroacetic acid → 2-Pyrimidinecarboxylic acid, 5-[[3-methyl-1-[4′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]butyl]amino]-, methyl ester

HRID 2406990

Reaction equation

HRID 2406990 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 679837782-Pyrimidinecarboxylic acid, 5-[[3-methyl-1-[4′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]butyl]amino]-, 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, 2 H) 7.67-7.73 (m, 2 H) 7.61-7.66 (m, 2 H) 7.56 (d, J=8.2 Hz, 2 H) 7.39 (d, J=8.2 Hz, 2 H) 4.68 (d, J=5.7 Hz, 1 H) 4.46-4.57 (m, 1 H) 3.98 (s, 3 H) 1.79-1.92 (m, 1 H) 1.64-1.79 (m, 2 H) 1.05 (d, J=6.2 Hz, 3 H) 0.99 (d, J=6.2 Hz, 3 H); 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-4514f271a9694e5984ef62a77352a8d9
Source dataset
uspto-grants-2014_08
Patent number
US08809342B2

Linked notes

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