Diisopropylethylamine → HCID 86663701, compound

HRID 2044050Notes

Reaction equation

HRID 2044050 reaction equation
Cl[C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[CH:14][CH:13]=2)[N:3]=1.Cl.[CH3:26][C:27]1[N:28]=[C:29]([NH:32][C:33]([NH:35][C@@H:36]2[CH2:41][CH2:40][CH2:39][NH:38][CH2:37]2)=[O:34])[S:30][CH:31]=1.CCN(C(C)C)C(C)C>CN1CCCC1=O>[CH3:24][N:21]1[CH2:22][CH2:23][N:18]([C:15]2[CH:16]=[CH:17][C:12]([NH:11][C:4]3[N:3]=[C:2]([N:38]4[CH2:39][CH2:40][CH2:41][C@@H:36]([NH:35][C:33]([NH:32][C:29]5[S:30][CH:31]=[C:27]([CH3:26])[N:28]=5)=[O:34])[CH2:37]4)[CH:10]=[CH:9][C:5]=3[C:6]([NH2:8])=[O:7])=[CH:13][CH:14]=2)[CH2:19][CH2:20]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 57489605HCID 57489605, compoundHCID 86663702HCID 86663702, compound

Product 1

HCID 86663701HCID 86663701, compoundYield 23.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 6-chloro-2-(4-(4-methylpiperazin-1-yl)phenylamino)nicotinamide (60 mg, 0.173 mmol), (R)-1-(4-methylthiazol-2-yl)-3-(piperidin-3-yl)urea hydrochloride (96 mg, 0.347 mmol), and DIEA (0.182 mL, 1.041 mmol) in N-methyl-2-pyrrolidinone (2 mL) was heated at 120° C. overnight. The reaction mixture was quenched with water, resulting in the formation of light brown precipitate. The solid was filtered, washed with water, and dried under vacuum. The residue was purified by MPLC chromatography (ISCO, 7% NH4OH/MeOH/CH2Cl2, 40 g silica gel column) to give 22 mg of (R)-2-(4-(4-methylpiperazin-1-yl)phenylamino)-6-(3-(3-(4-methylthiazol-2-yl)ureido)piperidin-1-yl)nicotinamide as a yellow solid. LCMS: (M+H)+=550.08; 1H NMR (400 MHz, CDCl3) δ ppm 10.62 (1H, s), 7.47 (2H, d, J=9.23 Hz), 7.33 (1H, d, J=8.79 Hz), 6.85 (2H, d, J=9.23 Hz), 6.28 (1H, s), 5.91 (1H, d, J=8.79 Hz), 5.69 (2H, br. s.), 4.00 (1H, d, J=7.47 Hz), 3.65-3.79 (2H, m), 3.55-3.64 (1H, m), 3.40-3.50 (1H, m), 3.07-3.14 (4H, m), 2.52-2.58 (4H, m), 2.33 (3H, s), 2.19 (3H, s), 1.87-1.98 (1H, m), 1.55-1.82 (3H, m).

Workup

  1. customThe reaction mixture was quenched with water
  2. customresulting in the formation of light brown precipitate
  3. filtrationThe solid was filtered
  4. washwashed with water
  5. customdried under vacuum
  6. customThe residue was purified by MPLC chromatography (ISCO, 7% NH4OH/MeOH/CH2Cl2, 40 g silica gel column)

Sources & evidence

ORD record
ord-78d3b008077441f8b84367e782980f64
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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