Pyridine → HCID 58902258, compound

HRID 1640220Notes

Reaction equation

HRID 1640220 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]([N:31]=[C:32]=[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].[CH3:34][C:35]1([CH3:42])[O:39][C@@H:38]([CH2:40][OH:41])[CH2:37][O:36]1.N1C=CC=CC=1>C1COCC1.CCOC(C)=O.CC1(C)O[C@@H](CO)CO1>[C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12]([CH:14]2[CH2:15][C:16]3[CH:17]=[C:18]([O:24][C:25]4[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32](=[O:33])[O:41][CH2:40][C@H:38]5[CH2:37][O:36][C:35]([CH3:42])([CH3:34])[O:39]5)[CH:26]=4)[CH:19]=[CH:20][C:21]=3[CH2:22][CH2:23]2)=[O:13])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 1049Pyridine3×HCID 736057(+)-SolketalHCID 58902371HCID 58902371, compound

Product 1

HCID 58902258HCID 58902258, compoundYield 90.3%

Reagents, catalysts & solvents 3

HCID 736057(+)-SolketalCatalyst2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of N-(3-tert-butylphenyl)-7-[(2-isocyanatopyridin-4-yl)oxy]-1,2,3,4-tetrahydronaphthalene-2-carboxamide (250 mg, 0.56 mmol), [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol (150 mg, 1.13 mmol) and pyridine (0.091 mL, 1.13 mmol) in THF (10 mL) was allowed to stir at rt. After 2 h, additional pyridine (0.14 mL) and [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol (0.220 mg) were added. The reaction mixture was heated at 70° C. overnight and then another portion of pyridine (0.10 mL) and [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol (0.150 mg g) were added. Heating continued for an additional 2 h and then the reaction mixture was subjected to MWI at 135° C. for 5 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give [(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl {4-[(7-{[(3-tert-butylphenyl)amino]carbonyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-oxy]pyridin-2-yl}carbamate (290 mg, 89%) as a white solid. LCMS: (FA) ES+574.4.

Workup

  1. temperatureThe reaction mixture was heated at 70° C. overnight
  2. temperatureHeating
  3. waitcontinued for an additional 2 h
  4. waitthe reaction mixture was subjected to MWI at 135° C. for 5 min
  5. washwashed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-4cb6c0d0aacc449f956554ef0dc2309b
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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