Hydrochloric Acid → (R)-5-(3-aminopiperidin-1-yl)-3-(4-(morpholine-4-carbonyl)phenylamino)pyrazine-2-carboxamide hydrochloride

HRID 1050516Notes

Reaction equation

HRID 1050516 reaction equation
[C:1]([C:4]1[N:5]=[CH:6][C:7]([N:25]2[CH2:30][CH2:29][CH2:28][C@@H:27]([NH:31]C(=O)OC(C)(C)C)[CH2:26]2)=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[O:18])=[CH:13][CH:12]=1)(=[O:3])[NH2:2].[ClH:39]>O1CCOCC1>[ClH:39].[NH2:31][C@@H:27]1[CH2:28][CH2:29][CH2:30][N:25]([C:7]2[N:8]=[C:9]([NH:10][C:11]3[CH:12]=[CH:13][C:14]([C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])=[CH:15][CH:16]=3)[C:4]([C:1]([NH2:2])=[O:3])=[N:5][CH:6]=2)[CH2:26]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 118115269US9656988, Example 73

Product 1

HCID 118115176(R)-5-(3-aminopiperidin-1-yl)-3-(4-(morpholine-4-carbonyl)phenylamino)pyrazine-2-carboxamide hydrochloride

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (R)-tert-butyl 1-(5-cyano-6-(4-(morpholine-4-carbonyl)phenylamino)pyrazin-2-yl)piperidin-3-ylcarbamate (88) in MeOH (15 mL) and DMSO (1.5 mL) was added solid NaOH (200 mg) and 30% H2O2 (1.5 mL). The mixture was stirred at RT for 20 min, diluted with acetonitrile (10 mL), and EtOAc (200 mL) 10 min later. The organic phase was washed with water ×2, dried, and concentrated in vacuo. The residue was subjected to flash column chromatography with 0 to 7% MeOH in DCM to isolate (R)-tert-butyl 1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyrazin-2-yl)piperidin-3-ylcarbamate (89) (yield >95%). (R)-tert-butyl 1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyrazin-2-yl)piperidin-3-ylcarbamate (89) was treated with 4N HCl in dioxane (30 mL) for 40 min. The mixture was concentrated in vacuo to dryness to afford (R)-5-(3-aminopiperidin-1-yl)-3-(4-(morpholine-4-carbonyl)phenylamino)pyrazine-2-carboxamide hydrochloride (90).

Workup

  1. concentrationThe mixture was concentrated in vacuo to dryness

Sources & evidence

ORD record
ord-112952995d294b608036640db597c77a
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

Loading…