Ethyl isocyanate → HCID 58902434, compound

HRID 1640184Notes

Reaction equation

HRID 1640184 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([NH:13][C:14]([CH:16]2[CH2:25][C:24]3[CH:23]=[C:22]([O:26][C:27]4[CH:32]=[CH:31][N:30]=[C:29]([C:33]([NH:35][CH3:36])=[O:34])[CH:28]=4)[CH:21]=[CH:20][C:19]=3[CH2:18][CH2:17]2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[N:37]([CH2:40][CH3:41])=[C:38]=[O:39]>C1COCC1.O>[CH2:40]([NH:37][C:38]([NH:1][CH2:2][C:3]1[CH:4]=[C:5]([NH:13][C:14]([CH:16]2[CH2:25][C:24]3[CH:23]=[C:22]([O:26][C:27]4[CH:32]=[CH:31][N:30]=[C:29]([C:33]([NH:35][CH3:36])=[O:34])[CH:28]=4)[CH:21]=[CH:20][C:19]=3[CH2:18][CH2:17]2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1)=[O:39])[CH3:41]

Participants

5

Reactant 2

HCID 8022Ethyl isocyanateHCID 23585320HCID 23585320, compound

Product 1

HCID 58902434HCID 58902434, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-{[7-({[3-(aminomethyl)-5-(trifluoromethyl)phenyl]amino}-carbonyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}-N-methylpyridine-2-carboxamide (0.411 g, 0.824 mmol) and TEA (0.23 mL, 1.65 mmol) in THF (10 mL) was added isocyanatoethane (0.10 mL, 1.26 mmol) in THF (5 mL) dropwise. The reaction mixture was allowed to stir at rt overnight. The reaction mixture was diluted with water and extracted with DCM. The organic solutions were combined, washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography and then converted to the HCl salt of 4-{[7-({[3-({[(ethylamino)carbonyl]amino}methyl)-5-(trifluoromethyl)phenyl]amino}carbonyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}-N-methylpyridine-2-carboxamide I-420. 1H NMR (400 MHz, d6-DMSO; HCl salt) δ: 10.42 (s, 1H), 8.84 (dd, 1H), 0.51 (dd, 1H), 8.03 (s, 1H), 7.68 (s, 1H), 7.41 (dd, 1H), 7.22-7.26 (m, 2H), 7.17 (dd, 1H), 7.01 (dd, 1H), 7.96 (dd, 1H), 4.23 (s, 2H), 3.01 (dd, 2H), 2.94 (dd, 2H), 2.80-2.90 (m, 3H), 2.77 (dd, 3H), 2.08-2.14 (m, 1H), 1.75-1.86 (m, 1H), and 0.98 (dd, 3H). LCMS: (FA) ES+ 570.7, ES− 568.4.

Workup

  1. extractionextracted with DCM
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-cdb6a84d95fc43b89e37625b38b79f45
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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