Water → HCID 58902453, compound

HRID 1640209Notes

Reaction equation

HRID 1640209 reaction equation
O=[C:2]1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][C:13]([NH:15][CH2:16][C:17]1[CH:18]=[C:19]([NH:27][C:28]([CH:30]2[CH2:39][C:38]3[CH:37]=[C:36]([O:40][C:41]4[CH:46]=[CH:45][N:44]=[C:43]([C:47]([NH:49][CH3:50])=[O:48])[CH:42]=4)[CH:35]=[CH:34][C:33]=3[CH2:32][CH2:31]2)=[O:29])[CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1)=[O:14].CN.O>CCO>[CH3:50][NH:49][C:47]([C:43]1[CH:42]=[C:41]([O:40][C:36]2[CH:35]=[CH:34][C:33]3[CH2:32][CH2:31][CH:30]([C:28]([NH:27][C:19]4[CH:20]=[C:21]([C:23]([F:25])([F:26])[F:24])[CH:22]=[C:17]([CH2:16][NH:15][C:13](=[O:14])[CH2:12][NH:3][CH3:2])[CH:18]=4)=[O:29])[CH2:39][C:38]=3[CH:37]=2)[CH:46]=[CH:45][N:44]=1)=[O:48]

Participants

5

Reactant 3

HCID 962WaterHCID 6329MethylamineHCID 58902254HCID 58902254, compound

Product 1

HCID 58902453HCID 58902453, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 4-{[7-({[3-({[(1,3dioxo-1,3-dihydro-2-H-isoindol-2-yl)acetyl]-amino}methyl)-5-(trifluoromethyl)phenyl]amino}carbonyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-oxy}-N-methylpyridine-2-carboxamide (0.819 g, 1.19 mmol) in EtOH (20 mL) was added a 40% aqueous solution of methyl amine in water (5.00 mL, 44.8 mmol). The reaction mixture was allowed to stir at rt for 5 h and then concentrated. The residue was purified by column chromatography to give N-methyl-4-{[7-({[3-({[(methylamino)acetyl]amino}-methyl)-5-(trifluoromethyl)phenylamino}carbonyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}-pyridine-2-carboxamide I-345 (0.124 g, 19%) as a white solid. 1H NMR (400 MHz, d6-DMSO, HCI salt) δ: 10.65 (s, 1H), 9.19-9.09 (br s, 1H), 8.85-8.77 (m, 1H), 8.50 (d, 1H), 8.17-8.02 (m, 2H), 7.66 (s, 1H), 7.41-7.36 (m, 1H), 7.28-7.21 (m, 1H), 7.19-7.14 (m, 1H), 7.04-6.94 (m, 2H), 4.22 (t, 2H), 3.83-3.76 (m, 2H), 3.67 (t, 2H), 3.03-2.81 (m, 5H), 2.77 (d, 3H), 2.17-2.08 (m, 1H), and 1.89-1.75 (m, 1H). LCMS: (FA) ES+543.2, ES−541.2.

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by column chromatography
  3. customto give N-methyl-4-{[7-({[3-({[(methylamino)acetyl]amino}-methyl)-5-(trifluoromethyl)phenylamino}carbonyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}-pyridine-2-carboxamide

Sources & evidence

ORD record
ord-6315294882934dc784f87345b238d870
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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