1,1'-Carbonyldiimidazole → N-(1-(5-carbamoylpyridin-2-yl)piperidin-4-yl)-4-isopropylpiperazine-1-carboxamide

HRID 1504599Notes

Reaction equation

HRID 1504599 reaction equation
Cl.[NH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([NH2:15])=[O:14])=[CH:11][N:10]=2)[CH2:5][CH2:4]1.[CH3:18][CH2:19][N:20]([CH:24]([CH3:26])[CH3:25])[CH:21](C)[CH3:22].[C:27](N1C=CN=C1)([N:29]1C=CN=C1)=[O:28].C(N1CCNCC1)(C)C>CN(C=O)C>[C:13]([C:12]1[CH:16]=[CH:17][C:9]([N:6]2[CH2:5][CH2:4][CH:3]([NH:2][C:27]([N:29]3[CH2:22][CH2:21][N:20]([CH:24]([CH3:26])[CH3:25])[CH2:19][CH2:18]3)=[O:28])[CH2:8][CH2:7]2)=[N:10][CH:11]=1)(=[O:14])[NH2:15]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 780131-IsopropylpiperazineHCID 81531DiisopropylethylamineHCID 693590386-(4-Aminopiperidin-1-yl)nicotinamide hydrochloride

Product 1

HCID 86730057N-(1-(5-carbamoylpyridin-2-yl)piperidin-4-yl)-4-isopropylpiperazine-1-carboxamideYield 8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled solution (0-5° C.) of 6-(4-aminopiperidin-1-yl)nicotinamide hydrochloride (293 mg, 1 mmol) in 5 ml DMF was added DIPEA (645 mg, 2.2 mmol) and 1,1′-carbonyldiimidazole (170 mg, 1.05 mmol). After stirring for 1 h, 1-isopropylpiperazine (154 mg, 1.2 mmol) was added and the resulting mixture was warmed to room temperature for 16 h. The crude mixture was filtered through Celite and the filtrate was purified by preparative HPLC to give title compound (30 mg, 8%) as an off-white solid. [1HNMR (400 MHz, DMSO-d6) δ 8.60 (d, 1H), 7.94 (m, 1H), 7.73 (s, 1H), 7.10 (s, 1H), 6.86 (d, 1H), 6.21 (d, 1H), 4.37 (d, 2H), 3.65 (m, 1H), 3.23 (t, 4H), 2.94 (t, 2H) 2.62 (m, 1H), 2.34 (t, 4H), 1.78 (d, 2H), 1.36 (m, 2H), 0.96 (d, 6H); LCMS RtB=1.53 min, [M+H]+=375.2].

Workup

  1. filtrationThe crude mixture was filtered through Celite
  2. customthe filtrate was purified by preparative HPLC

Sources & evidence

ORD record
ord-d6668632bbc64f18b9250b2827ba5cc7
Source dataset
uspto-grants-2015_12
Patent number
US09216182B2

Reaction notes

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