p-Toluenesulfonic acid → HCID 349055, compound

HRID 1640218Notes

Reaction equation

HRID 1640218 reaction equation
C(NC1C=C(O[C:12]2[CH:21]=[C:20]3[C:15]([CH2:16][CH2:17][CH:18]([C:22]([NH:24]C4C=C(C(F)(F)F)C=C(OC[C@H]5COC(C)(C)O5)C=4)=[O:23])[CH2:19]3)=[CH:14][CH:13]=2)C=CN=1)(=O)C.CC1C=CC(S(O)(=O)=O)=CC=1>CO.O>[CH2:19]1[C:20]2[C:15](=[CH:14][CH:13]=[CH:12][CH:21]=2)[CH2:16][CH2:17][CH:18]1[C:22]([NH2:24])=[O:23]

Participants

5

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 58902305HCID 58902305, compound

Product 1

HCID 349055HCID 349055, compoundYield 285.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

A mixture of 7-{[2-(acetylamino)pyridin-4-yl]oxy}-N-[3-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-5-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide (100 mg, 0.16 mmol) and pTSA (28 mg, .16 mmol) in MeOH (7 mL) and water (1 mL) was allowed to stir at rt overnight and then at 70° C. Water was added and the mixture was extracted with EtOAc. The organic solutions were combined, washed with sat. aq. NaHCO3 and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give 7-{[2-(acetylamino)pyridin-4-yl]oxy}-N-3-{[(2R)-2,3-dihydroxypropyl]-oxy}-5-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide (I-412) (80 mg, 68%) as a white solid. 1H NMR (400 MHz, d6-DMSO, HCl salt) δ: 10.52 (s, 1H), 8.24 (d, 1H), 7.66 (br s, 1H), 7.56 (br s, 1H), 7.29-7.17 (m, 2H), 7.06-6.86 (m, 4H), 4.07-3.75 (m, 3H), 3.46-3.40 (m, 2H), 3.00-2.74 (m, 5H), 2.19-2.05 (m, 4H), and 1.89-1.71 (m, 1H). LCMS: (FA) ES+560.1, ES−558.0.

Workup

  1. customat 70° C
  2. extractionthe mixture was extracted with EtOAc
  3. washwashed with sat. aq. NaHCO3 and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-f8f60885da1e4c8e8d713840cb4833ff
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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