Trifluoroacetic acid methylene chloride → HCID 118114781, compound

HRID 1050541Notes

Reaction equation

HRID 1050541 reaction equation
[C:1]([C:4]1[C:5]([NH:22][C:23]2[CH:24]=[N:25][N:26]([CH:28]3[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]3)[CH:27]=2)=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH2:13][C@@H:12]([NH:16][C:17]([N:19]([CH3:21])[CH3:20])=[O:18])[CH2:11]2)=[CH:8][N:9]=1)(=[O:3])[NH2:2].C(Cl)Cl.C(O)(C(F)(F)F)=O>>[CH3:20][N:19]([CH3:21])[C:17](=[O:18])[NH:16][C@@H:12]1[CH2:13][CH2:14][CH2:15][N:10]([C:7]2[N:6]=[C:5]([NH:22][C:23]3[CH:24]=[N:25][N:26]([CH:28]4[CH2:29][CH2:30][NH:31][CH2:32][CH2:33]4)[CH:27]=3)[C:4]([C:1]([NH2:2])=[O:3])=[N:9][CH:8]=2)[CH2:11]1

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 118115761HCID 118115761, compound

Product 1

HCID 118114781HCID 118114781, compound

Procedure

Crude (R)-tert-butyl 4-(4-(3-carbamoyl-6-(3-(3,3-dimethylureido)piperidin-1-yl)pyrazin-2-ylamino)-1H-pyrazol-1-yl)piperidine-1-carboxylate (277, 72 mg, 0.13 mmol) was treated with 2:1 DCM/TFA at RT for 1 hour and concentrated in vacuo to get (R)-5-(3-(3,3-dimethylureido)piperidin-1-yl)-3-(1-(piperidin-4-yl)-1H-pyrazol-4-ylamino)pyrazine-2-carboxamide (278) TFA salt. It was dissolved in 4 mL NMP. To it were added DIEA (230 μL, 1.3 mmol) and cyclopropanecarbobyl chloride (41 mg, 0.39 mmol). The mixture was stirred at RT for 2 hours, acidified with 0.5 mL TFA, and directly subjected to reverse phase prep HPLC using 5 mM HCl (aq) and neat MeCN as mobile phases to isolate (R)-3-(1-(1-(cyclopropanecarbonyl)piperidin-4-yl)-1H-pyrazol-4-ylamino)-5-(3-(3,3-dimethylureido)piperidin-1-yl)pyrazine-2-carboxamide (280) as HCl salt (32 mg, 47%). MS found for C25H36N10O3 as (M+H)+ 525.5, (M−H)− 523.3. UV: λ=253, 269, 298, 331, 374 nm.

Workup

  1. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e6243f0266b84629a09af6b09a191afe
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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