Ammonium Chloride → 1-[4-(3-{[4-(Trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxamide

HRID 1028150Notes

Reaction equation

HRID 1028150 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]2[CH:11]=[C:12]([C:16]3[N:17]=[C:18]([N:21]4[CH2:26][CH2:25][CH:24]([C:27](O)=[O:28])[CH2:23][CH2:22]4)[S:19][CH:20]=3)[CH:13]=[CH:14][CH:15]=2)[N:4]=1.[Cl-].[NH4+].C([N:37](C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]([F:31])([F:30])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]2[CH:11]=[C:12]([C:16]3[N:17]=[C:18]([N:21]4[CH2:22][CH2:23][CH:24]([C:27]([NH2:37])=[O:28])[CH2:25][CH2:26]4)[S:19][CH:20]=3)[CH:13]=[CH:14][CH:15]=2)[N:4]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 683241951-[4-(3-{[4-(Trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylic acid

Product 1

HCID 672365141-[4-(3-{[4-(Trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxamideYield 22.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylic acid (36 mg, 0.08 mmol) in N,N-dimethylformamide (0.8 mL) was added ammonium chloride (13 mg, 0.24 mmol), diisopropylethylamine (56 L, 0.32 mmol), and (1H-benzotriazol-1-yloxy)(tripyrrolidin-1-yl)phosphonium hexafluorophosphate (83 mg, 0.16 mmol). The mixture was stirred for 60 minutes at room temperature. The mixture was diluted with ethyl acetate (30 mL), and washed with 1:1 saturated sodium bicarbonate:brine (30 mL), and 1:1 water:brine (30 mL). The aqueous fractions were further extracted with ethyl acetate (30 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by reverse phase HPLC to provide 8 mg (0.018 mmol, 22% yield) of 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxamide as a white solid. MS APCI: [M+H]+ m/z 449.1. 1H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.84 (d, J=4.8 Hz, 1H), 8.01 (s, 1H), 7.55-7.51 (m, 2H), 7.35-7.29 (m, 3H), 7.16 (d, J=7.6 Hz, 1H), 6.84 (s, 1H), 3.93 (m, 2H), 3.09 (m, 2H), 2.37 (m, 1H), 1.97-1.70 (m, 2H), 1.62 (m, 2H). rhSyk=++.

Workup

  1. washwashed with 1:1 saturated sodium bicarbonate
  2. extractionThe aqueous fractions were further extracted with ethyl acetate (30 mL)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-c0e86ca9902b47e993baeeb1451495c9
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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