Propionyl chloride → HCID 118115243, compound

HRID 1050598Notes

Reaction equation

HRID 1050598 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[N:9]=[C:10]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([CH:24]4[CH2:29][CH2:28][N:27]([CH:30]5[CH2:34][CH2:33][CH2:32][CH2:31]5)[CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=2)[CH2:3]1.CCN(C(C)C)C(C)C.[C:44](Cl)(=[O:47])[CH2:45][CH3:46]>CN1C(=O)CCC1>[CH:30]1([N:27]2[CH2:28][CH2:29][CH:24]([C:21]3[CH:20]=[CH:19][C:18]([NH:17][C:10]4[C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=[C:8]([N:4]5[CH2:5][CH2:6][CH2:7][C@@H:2]([NH:1][C:44](=[O:47])[CH2:45][CH3:46])[CH2:3]5)[N:9]=4)=[CH:23][CH:22]=3)[CH2:25][CH2:26]2)[CH2:31][CH2:32][CH2:33][CH2:34]1

Participants

5

Reactant 3

HCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 118114439HCID 118114439, compound

Product 1

HCID 118115243HCID 118115243, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

(R)-5-(3-Aminopiperidin-1-yl)-3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazine-2-carboxamide (436) (40 mg, 0.075 mmol) was dissolved in 3 mL NMP. To it were added DIEA (80 μL, 0.45 mmol) and then propionyl chloride (20 μL, 0.23 mmol). The mixture was stirred at RT for 30 min, quenched with 0.3 mL TFA, and directly subjected to reverse phase preparative HPLC using 5 mM HCl (aq) and nest MeCN to isolate the title compound, (R)-3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)-5-(3-propionamidopiperidin-1-yl)pyrazine-2-carboxamide (438), as HCl salt (23 mg). LC-MS (ESI): m/z (M+1) 520.6. UV: λ=267, 276, 305, 335, 372 nm. Proton NMR (CD3OD): δ 7.62 (1H, s), 7.59 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz), 4.19 (1H, m), 4.01 (1H, m), 3.91 (1H, m), 3.72 (2H, d, J=12.0 Hz), 3.55 (1H, m), 3.42 (1H, m), 3.38 (1H, m), 3.12 (2H, m), 2.86 (1H, m), 2.22-1.64 (18H, m), 1.12 (3H, t, J=7.5 Hz) ppm.

Workup

  1. customquenched with 0.3 mL TFA

Sources & evidence

ORD record
ord-dd9ad082419b41638dcde483cec98537
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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