1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-{1-[1-(1-Methyl-cyclopropanecarbonyl)-piperidin-4-yloxy] isoquinolin-4-yl}-3-[5-(1-methyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea

HRID 729625Notes

Reaction equation

HRID 729625 reaction equation
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.Cl.[CH3:24][C:25]1([C:28]2[CH:29]=[C:30]([NH:40][C:41]([NH:43][C:44]3[C:53]4[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=4)[C:47]([O:54][CH:55]4[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]4)=[N:46][CH:45]=3)=[O:42])[N:31]([C:33]3[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=3)[N:32]=2)[CH2:27][CH2:26]1.[CH3:61][C:62]1([C:65](O)=[O:66])[CH2:64][CH2:63]1.CCN(C(C)C)C(C)C>ClCCl>[CH3:61][C:62]1([C:65]([N:58]2[CH2:59][CH2:60][CH:55]([O:54][C:47]3[C:48]4[C:53](=[CH:52][CH:51]=[CH:50][CH:49]=4)[C:44]([NH:43][C:41]([NH:40][C:30]4[N:31]([C:33]5[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=5)[N:32]=[C:28]([C:25]5([CH3:24])[CH2:27][CH2:26]5)[CH:29]=4)=[O:42])=[CH:45][N:46]=3)[CH2:56][CH2:57]2)=[O:66])[CH2:64][CH2:63]1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 813261-Methylcyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 690540351-[5-(1-Methyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]-3-[1-(piperidin-4-yloxy)-isoquinolin-4-yl]-urea dihydrochloride

Product 1

HCID 160614691-{1-[1-(1-Methyl-cyclopropanecarbonyl)-piperidin-4-yloxy] isoquinolin-4-yl}-3-[5-(1-methyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Place EDCI (0.147 g, 0.77 mmol), HOBt (0.10 g, 0.77 mmol), 1-[5-(1-methyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]-3-[1-(piperidin-4-yloxy)-isoquinolin-4-yl]-urea dihydrochloride (Preparation 3, 0.16 g, 0.64 mmol) and 1-methyl-1-cyclopropyl carboxylic acid (1.1 eq) in a flask under N2. Add dichloromethane (5 mL) follow by DIPEA (0.22 mL, 1.28 mmol) and stir at room temperature overnight. Evaporate solvent to give a residue. Subject residue to silica gel chromatography eluting with hexane:AcOEt 50-100% to give 1-{1-[1-(1-methyl-cyclopropanecarbonyl)-piperidin-4-yloxy]-isoquinolin-4-yl}-3-[5-(1-methyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea as a free base. ES+ (m/z) 579.3 (M+H).

Workup

  1. customEvaporate solvent to give a residue
  2. washSubject residue to silica gel chromatography eluting with hexane

Sources & evidence

ORD record
ord-4e56b36a41174fb083624dc00983c61a
Source dataset
uspto-grants-2009_09
Patent number
US07582638B2

Reaction notes

Loading…