Hydrochloric Acid → HCID 58902288, compound

HRID 1640206Notes

Reaction equation

HRID 1640206 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12]([CH:14]2[CH2:23][CH2:22][C:21]3[C:16](=[CH:17][C:18]([O:24][C:25]4[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32]([NH:34][CH2:35][CH2:36][CH2:37]Cl)=[O:33])[CH:26]=4)=[CH:19][CH:20]=3)[CH2:15]2)=[O:13])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].Cl>C(O)(C)(C)C>[C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12]([CH:14]2[CH2:23][CH2:22][C:21]3[C:16](=[CH:17][C:18]([O:24][C:25]4[CH:30]=[CH:29][N:28]=[C:27]([N:31]5[CH2:37][CH2:36][CH2:35][NH:34][C:32]5=[O:33])[CH:26]=4)=[CH:19][CH:20]=3)[CH2:15]2)=[O:13])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 58902299HCID 58902299, compound

Product 1

HCID 58902288HCID 58902288, compound

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of N-(3-tert-butylphenyl)-7-{[2-({[(3-chloropropyl)amino-]carbonyl}-amino)pyridin-4-yl]oxy}-1,2,3,4-tetrahydronaphthalene-2-carboxamide (0.71 g, 1.3 mmol) in tert-butyl alcohol (15 mL) was added potassium tert-butoxide (1M in THF, 4 mL). The reaction mixture was heated at 30° C. for 12 h and then acidified with 1N HCl and concentrated. The residue was redissolved in water and DCM and the aqueous solution was further extracted with DCM. The combined organic solutions were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography. To a solution of the resulting product in MeOH, was added a 1N solution of HCl in Et2O (2 mL). The solvent was evaporated to give N-(3-tert-butylphenyl)-7-{[2-(2-oxotetrahydropyrimidin-1(2H)-yl)-pyridin-4-yl]oxy}-1,2,3,4-tetrahydronaphthalene-2-carboxamide I-408 as the HCl salt (0.304 g, 46%). 1H NMR (400 MHz, d6-DMSO, HCl salt) δ: 10.04 (s, 1H), 8.28 (d, 1H), 7.65 (t, 1H), 7.53-7.62 (br s, 1H), 7.48-7.53 (m, 1H), 7.29-7.32 (m, 1H), 7.17-7.26 (m, 2H), 7.04-7.08 (m, 1H), 7.00-7.04 (m, 1H), 6.94-6.99 (m, 1H), 6.77-6.82 (m, 1H), 3.81 (t, 2H), 3.21 (t, 2H), 2.74-2.97 (m, 5H), 2.05-2.13 (m, 1H), 1.95 (t, 2H), 1.70-1.83 (m, 1H), and 1.25 (s, 9H). LCMS: (FA) ES+499.7, ES−497.0.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was redissolved in water
  3. extractionDCM and the aqueous solution was further extracted with DCM
  4. washThe combined organic solutions were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography
  9. additionTo a solution of the resulting product in MeOH, was added a 1N solution of HCl in Et2O (2 mL)
  10. customThe solvent was evaporated

Sources & evidence

ORD record
ord-8cd7642cabb94918a9005f6896e415c6
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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