Trifluoroacetic acid → 5-Fluoro-2-{4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinyl}pyrimidine

HRID 423620Notes

Reaction equation

HRID 423620 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:16]=[CH:15][C:14]([O:17][CH2:18][CH:19]3[CH2:24][CH2:23][N:22]([C:25](OC(C)(C)C)=O)[CH2:21][CH2:20]3)=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[K+].[K+].ClC1[N:51]=[CH:50][C:49]([F:52])=[CH:48][N:47]=1>C(Cl)Cl.CS(C)=O>[F:52][C:49]1[CH:48]=[N:47][C:25]([N:22]2[CH2:23][CH2:24][CH:19]([CH2:18][O:17][C:14]3[CH:15]=[N:16][C:11]([C:8]4[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:10][CH:9]=4)=[CH:12][CH:13]=3)[CH2:20][CH2:21]2)=[N:51][CH:50]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 5834662-Chloro-5-fluoropyrimidineHCID 249943331,1-Dimethylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate

Product 1

HCID 591778185-Fluoro-2-{4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinyl}pyrimidine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

The title compound (91 mg, 84%) was prepared as a white solid from 1,1-dimethylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate (prepared as in Example 150, Step 2, 0.11 g, 0.25 mmol) and TFA (0.20 mL) in CH2Cl2 (6 mL) then K2CO3 (0.75 g) and 2-chloro-5-fluoropyrimidine (47 μL, 0.27 mmol) in DMSO (5 mL) in a manner similar to Example 80. The crude material was purified by chromatography on a silica gel column eluted with 1:15 acetone/CH2Cl2 to give the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.42 (d, 1H, J=2.7 Hz), 8.18 (s, 2H), 8.14 (d, 2H, J=8.3 Hz), 8.02 (d, 2H), J=8.3 Hz), 7.76 (d, 1H, J=8.8 Hz), 7.45-7.35 (m, 1H), 4.80-4.70 (m, 2H), 3.94 (d, 2H, J=6.1 Hz), 3.07 (s, 3H), 3.00-2.85 (m, 2H), 2.10-2.05 (m, 1H), 2.00-1.90 (m, 2H), 1.45-1.30 (m, 2H); LRMS (ESI), m/z 443 (M+H).

Workup

  1. customThe crude material was purified by chromatography on a silica gel column
  2. washeluted with 1:15 acetone/CH2Cl2

Sources & evidence

ORD record
ord-b8f90dd3fe514968835ead6ee1427e7f
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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