Trifluoroacetic acid → 1-(4-(Cyanomethyl)-1-((1-ethyl-1H-imidazol-2-yl)methyl)piperidin-4-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide

HRID 521228Notes

Reaction equation

FC(F)(F)C([O-])=O.[C:8]([C:11]1[C:12]([NH:25][C:26]2[CH:31]=[CH:30][N:29]=[C:28]([F:32])[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].[CH2:33]([N:35]1[CH:39]=[CH:38][N:37]=[C:36]1[CH:40]=O)[CH3:34].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(O)(C(F)(F)F)=O>CN(C=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:31]=[CH:30][N:29]=[C:28]([F:32])[CH:27]=3)=[N:13]2)[CH2:17][CH2:18][N:19]([CH2:40][C:36]2[N:35]([CH2:33][CH3:34])[CH:39]=[CH:38][N:37]=2)[CH2:20][CH2:21]1)#[N:24]

Participants

Conditions

Temperature: 50 °C

Procedure

To a reaction vial was added 4-{4-carbamoyl-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-4) (0.020 g, 0.058 mmol), 1-ethyl-1H-imidazole-2-carbaldehyde (0.0072 g, 0.058 mmol), Na(OAc)3BH (0.062 g, 0.29 mmol), TFA (0.030 g, 0.26 mmol) suspended in DMF (0.97 mL). The reaction vessel was sealed and heated to 50° C. with stirring for 12 hours. The completed reaction was directly purified by reverse phase preparative HPLC (using a gradient elution of 0-95% ACN/water with 0.1% v/v NH4OH modifier) to afford the title compound, Example #22-1.

Workup

customThe reaction vessel was sealed
customThe completed reaction
customwas directly purified by reverse phase preparative HPLC (
washa gradient elution of 0-95% ACN/water with 0.1% v/v NH4OH modifier)

Sources & evidence

ORD record: ord-763ecf1e5433480c8c8f579cdde4b244
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328099B2

Reaction notes

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