Diisopropylethylamine → 1-[4-(Cyanomethyl)-1-pyrimidin-4-ylpiperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide

HRID 521232Notes

Reaction equation

HRID 521232 reaction equation
FC(F)(F)C([O-])=O.[C:8]([C:11]1[C:12]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[N:13][N:14]([C:16]2([CH2:22][C:23]#[N:24])[CH2:21][CH2:20][NH2+:19][CH2:18][CH2:17]2)[CH:15]=1)(=[O:10])[NH2:9].CCN(C(C)C)C(C)C.Br[C:43]1[CH:48]=[CH:47][N:46]=[CH:45][N:44]=1>ClCCCl.C(Cl)Cl.CC(O)C>[C:23]([CH2:22][C:16]1([N:14]2[CH:15]=[C:11]([C:8]([NH2:9])=[O:10])[C:12]([NH:25][C:26]3[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=3)=[N:13]2)[CH2:21][CH2:20][N:19]([C:43]2[CH:48]=[CH:47][N:46]=[CH:45][N:44]=2)[CH2:18][CH2:17]1)#[N:24]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 127522204-BromopyrimidineHCID 867294014-(4-carbamoyl-3-((4-fluorophenyl)amino)-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidin-1-ium 2,2,2-trifluoroacetate2×

Product 1

HCID 867294031-[4-(Cyanomethyl)-1-pyrimidin-4-ylpiperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-5) (50 mg, 0.11 mmol) in DCE (1.0 mL) was added DIPEA (0.096 mL, 0.55 mmol) followed by 4-bromopyrimidine (32 mg, 0.16 mmol). The reaction mixture was heated under microwave irradiation to 130° C. and allowed to stir for 15 minutes. The reaction mixture was then cooled to ambient temperature and diluted with a mixture of DCM and IPA. The resulting mixture was sequentially washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The resulting residue was purified by reverse-phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, and concentrated in vacuo to afford the title compound, Example #26, as a solid.

Workup

  1. temperatureThe reaction mixture was then cooled to ambient temperature
  2. washThe resulting mixture was sequentially washed with water, brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by reverse-phase preparative HPLC (MeCN/water
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3ac2d48f348e48029c4522b5908a662c
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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