Dimethylcarbamoyl Chloride → Hydrochloric Acid

HRID 1050549Notes

Reaction equation

HRID 1050549 reaction equation
[CH3:1][N:2]([CH3:35])[C:3](=[O:34])[NH:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][N:7]([C:11]2[N:12]=[C:13]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]4([CH3:33])[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)=[CH:23][CH:22]=3)[C:14]([C:17]([NH2:19])=[O:18])=[N:15][CH:16]=2)[CH2:6]1.CCN(C(C)C)C(C)C.[CH3:45][N:46]([CH3:50])[C:47]([Cl:49])=[O:48]>CN1C(=O)CCC1>[CH3:45][N:46]([CH3:50])[C:47]([N:30]1[CH2:29][CH2:28][C:27]([C:24]2[CH:25]=[CH:26][C:21]([NH:20][C:13]3[C:14]([C:17]([NH2:19])=[O:18])=[N:15][CH:16]=[C:11]([N:7]4[CH2:8][CH2:9][CH2:10][C@@H:5]([NH:4][C:3]([N:2]([CH3:1])[CH3:35])=[O:34])[CH2:6]4)[N:12]=3)=[CH:22][CH:23]=2)([CH3:33])[CH2:32][CH2:31]1)=[O:48].[ClH:49]

Participants

6

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 81531DiisopropylethylamineHCID 118114473HCID 118114473, compound

Product 2

HCID 313Hydrochloric AcidYield 836.5%HCID 118115023HCID 118115023, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

(R)-5-(3-(3,3-Dimethylureido)piperidin-1-yl)-3-(4-(4-methylpiperidin-4-yl)phenylamino)pyrazine-2-carboxamide (289) (90 mg, 0.2 mmol) was dissolved in 4 mL NMP. To it were added DIEA (350 μL, 2.0 mmol) and then dimethylcarbamoyl chloride (55 μL, 0.6 mmol). The mixture was stirred at RT for 30 min, quenched 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-(4-(1-(dimethylcarbamoyl)-4-methylpiperidin-4-yl)phenylamino)-5-(3-(3,3-dimethylureido)piperidin-1-yl)pyrazine-2-carboxamide (291) as HCl salt (61 mg, 55%). MS found for C28H41N9O3 as (M+H)+ 552.4, (M−H)− 550.3. UV: λ=268, 277, 305, 336, 372 nm Proton NMR (CD3OD): δ 7.63 (1H, s), 7.61 (2H, d, J=8.5 Hz), 7.32 (2H, d, J=8.5 Hz), 4.37 (1H, m), 4.21 (1H, m), 3.77 (1H, m), 3.37-3.31 (2H, m), 3.21-3.15 (3H, m), 3.10 (1H, m), 2.88 (6H, s), 2.83 (6H, s), 2.15 (2H, m), 2.02 (1H, m), 1.87 (1H, m), 1.75-1.63 (4H, m), 1.26 (3H, s) ppm.

Workup

  1. customquenched with 0.5 mL TFA

Sources & evidence

ORD record
ord-c9f50e3b37e14d65a785e21f989b184d
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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