p-Toluenesulfonic acid → HCID 58902289, compound

HRID 1640221Notes

Reaction equation

HRID 1640221 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12]([CH:14]2[CH2:23][C:22]3[CH:21]=[C:20]([O:24][C:25]4[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32](=[O:42])[O:33][CH2:34][C@H:35]5[CH2:39][O:38]C(C)(C)[O:36]5)[CH:26]=4)[CH:19]=[CH:18][C:17]=3[CH2:16][CH2:15]2)=[O:13])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].CC1C=CC(S(O)(=O)=O)=CC=1>CO.O>[C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12]([CH:14]2[CH2:23][C:22]3[CH:21]=[C:20]([O:24][C:25]4[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32](=[O:42])[O:33][CH2:34][C@@H:35]([OH:36])[CH2:39][OH:38])[CH:26]=4)[CH:19]=[CH:18][C:17]=3[CH2:16][CH2:15]2)=[O:13])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 58902258HCID 58902258, compound

Product 1

HCID 58902289HCID 58902289, compoundYield 56.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of [(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, 0.50 mmol) and pTSA (87 mg, 0.50 mmol) in MeOH (10 mL) and water (1 mL) were heated at 70° C. for 56 h. The reaction mixture was concentrated; diluted with water, and 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 (2S)-2,3-dihydroxypropyl {4-[(7-{[(3-tert-butylphenyl)amino]carbonyl}-5,6,7,8-tetrahydronaphthalen-2-yl)oxy]pyridin-2-yl}carbamate (I-272) (150 mg, 55%) as a white solid. 1H NMR (400 MHz, CD3OD, HCl salt) δ: 9.86 (s, 1H), 8.21 (d, 1H), 7.65-7.62 (m; 1H), 7.43-7.38 (m, 1H), 7.31-7.20 (m, 2H), 7.17-7.14 (m, 1H), 7.11-7.06 (m, 1H), 7.04-6.97 (m, 2H), 6.70-6.67 (m, 1H), 4.40-4.25 (qq, 2H), 3.91-3.85 (m, 1H), 3.60-3.56 (m, 2H), 3.15-2.79 (m, 5H), 2.24-2.16 (m, 1H), 1.99-1.88 (m, 1H), and 1.31 (s, 9H). LCMS: (FA) ES+534.3, ES−532.6.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with water
  3. extractionextracted with EtOAc
  4. washwashed with sat. aq. NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-afcc0587e4984971b08f22c7a309ce40
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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