4-tert-Butylbenzoyl chloride → (R)-5-(3-(4-tert-butylbenzamido)piperidin-1-yl)-3-(4-(morpholine-4-carbonyl)phenylamino)pyrazine-2-carboxamide

HRID 1050517Notes

Reaction equation

HRID 1050517 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[N:10]=[C:11]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[O:26])=[CH:21][CH:20]=3)[C:12]([C:15]([NH2:17])=[O:16])=[N:13][CH:14]=2)[CH2:4]1.CCN(C(C)C)C(C)C.[C:42]([C:46]1[CH:54]=[CH:53][C:49]([C:50](Cl)=[O:51])=[CH:48][CH:47]=1)([CH3:45])([CH3:44])[CH3:43]>CN1C(=O)CCC1.CCOC(C)=O>[C:42]([C:46]1[CH:47]=[CH:48][C:49]([C:50]([NH:2][C@@H:3]2[CH2:8][CH2:7][CH2:6][N:5]([C:9]3[N:10]=[C:11]([NH:18][C:19]4[CH:20]=[CH:21][C:22]([C:25]([N:27]5[CH2:32][CH2:31][O:30][CH2:29][CH2:28]5)=[O:26])=[CH:23][CH:24]=4)[C:12]([C:15]([NH2:17])=[O:16])=[N:13][CH:14]=3)[CH2:4]2)=[O:51])=[CH:53][CH:54]=1)([CH3:45])([CH3:43])[CH3:44]

Participants

6

Reactant 3

HCID 743724-tert-Butylbenzoyl chlorideHCID 81531DiisopropylethylamineHCID 118115176(R)-5-(3-aminopiperidin-1-yl)-3-(4-(morpholine-4-carbonyl)phenylamino)pyrazine-2-carboxamide hydrochloride

Product 1

HCID 118114486(R)-5-(3-(4-tert-butylbenzamido)piperidin-1-yl)-3-(4-(morpholine-4-carbonyl)phenylamino)pyrazine-2-carboxamideYield 72.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of (R)-5-(3-aminopiperidin-1-yl)-3-(4-(morpholine-4-carbonyl)phenylamino)pyrazine-2-carboxamide hydrochloride (90) (120 mg, 0.27 mmol) in NMP (3 mL) was added DIEA (190 μL, 1.08 mmol) and then 4-tert-butylbenzoyl chloride (106 mg, 0.54 mmol). The mixture was stirred at RT for 1 h, diluted with 100 mL EtOAc, washed with water ×2, dried, and concentrated in vacuo. The residue was subjected to flash column chromatography with 0 to 5% MeOH in DCM to isolate the title compound (91) (yield 114 mg). MS found for C32H39N7O4 as (M+H)+ 586.2, (M−H)− 584.3. UV: λ=259, 276, 286, 314, 344, 369 nm.

Workup

  1. washwashed with water ×2
  2. customdried
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-69251721b96d4a6586a1100d9bf45dbe
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

Loading…