Formic Acid → HCID 118115372, compound

HRID 1050597Notes

Reaction equation

HRID 1050597 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.[CH:35](O)=[O:36].CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[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][CH:35]=[O:36])[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

6

Reactant 4

HCID 284Formic AcidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 118114439HCID 118114439, compound

Product 1

HCID 118115372HCID 118115372, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R)-5-(3-Aminopiperidin-1-yl)-3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazine-2-carboxamide (436) (50 mg, 0.1 mmol) was dissolved in 4 mL DMF. To it were added formic acid (20 μL, 0.5 mmol), DIEA (180 μL, 1.0 mmol) and then PyBOP (105 mg, 0.2 mmol). The mixture was stirred at RT for 2 hours, 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-formamidopiperidin-1-yl)pyrazine-2-carboxamide (437), as HCl salt (24 mg). LC-MS (ESI): m/z (M+1) 492.7. UV: λ=267, 276, 305, 335, 372 nm. Proton NMR (CD3OD): δ 8.06 (1H, s), 7.65 (1H, s), 7.58 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz), 4.19 (1H, m), 4.01 (1H, m), 3.93 (1H, m), 3.71 (2H, d, J=12.0 Hz), 3.54 (1H, m), 3.46 (1H, m), 3.38 (1H, m), 3.12 (2H, m), 2.86 (1H, m), 2.22-1.66 (16H, m) ppm.

Workup

  1. customquenched with 0.3 mL TFA

Sources & evidence

ORD record
ord-2e5f56fe4fc242169ebc3dff5d798eca
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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