Ammonium Chloride → HCID 53251706, compound

HRID 1028113Notes

Reaction equation

HRID 1028113 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[S:20][C:19]([N:21]4[CH2:26][CH2:25][CH:24]([C:27](O)=[O:28])[CH2:23][CH2:22]4)=[N:18][CH:17]=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.CCOC(C)=O>[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[S:20][C:19]([N:21]4[CH2:22][CH2:23][CH:24]([C:27]([NH2:37])=[O:28])[CH2:25][CH2:26]4)=[N:18][CH:17]=3)[CH:13]=[CH:14][CH:15]=2)[N:4]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 71075024HCID 71075024, compound

Product 1

HCID 53251706HCID 53251706, compoundYield 48.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylic acid (15 mg, 0.033 mmol) in N,N-dimethylformamide (0.33 mL) was added ammonium chloride (5.4 mg, 0.10 mmol), diisopropylethylamine (23 μL, 0.13 mmol) and then (1H-benzotriazol-1-yloxy)(tripyrrolidin-1-yl)phosphonium hexafluorophosphate (35 mg, 0.067 mmol). After stirring for 90 minutes at room temperature, the mixture was diluted with EtOAc (30 mL), then washed with 1:1 saturated aqueous sodium bicarbonate:brine (2×30 mL). The aqueous fractions were further extracted with EtOAc (30 mL). The combined organic extracts were dried over sodium sulfate, and concentrated under reduced pressure. Purification by reverse phase HPLC provided 7 mg (0.016 mmol, 47% yield) of 1-[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxamide. MS APCI: [M+H]+ m/z 449.1. 1H NMR (400 MHz, DMSO): δ 10.26 (s, 1H); 8.84 (d, J=4.9 Hz, 1H); 8.01 (s, 1H); 7.57-7.49 (m, 2H); 7.35-7.26 (m, 3H); 7.16 (d, J=7.7 Hz, 1H); 6.85 (s, 1H); 3.93 (d, J=12.8 Hz, 2H); 3.14-2.98 (m, 2H); 2.42-2.31 (m, 1H); 1.91-1.69 (m, 2H); 1.69-1.55 (m, 2H). rhSyk=+++.

Workup

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

Sources & evidence

ORD record
ord-3078e5e1feac46308888bd988ecc44d9
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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