Benzoyl isothiocyanate → N-{[(3S,4R,6R)-3-(5-bromo-2-fluorophenyl)-6-cyclopropyl-4-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]carbamothioyl}benzamide

HRID 68434Notes

Reaction equation

HRID 68434 reaction equation
[C:1]([N:9]=[C:10]=[S:11])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:12][C@@:13]1([C:24]2[CH:29]=[C:28]([Br:30])[CH:27]=[CH:26][C:25]=2[F:31])[CH2:18][O:17][C@@H:16]([CH:19]2[CH2:21][CH2:20]2)[CH2:15][C@H:14]1[CH2:22][OH:23]>ClCCl>[Br:30][C:28]1[CH:27]=[CH:26][C:25]([F:31])=[C:24]([C@@:13]2([NH:12][C:10]([NH:9][C:1](=[O:8])[C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[S:11])[C@H:14]([CH2:22][OH:23])[CH2:15][C@H:16]([CH:19]3[CH2:20][CH2:21]3)[O:17][CH2:18]2)[CH:29]=1

Participants

4

Reactant 2

HCID 68284Benzoyl isothiocyanateHCID 86721308[(2R,4R,5S)-5-amino-5-(5-bromo-2-fluorophenyl)-2-cyclopropyltetrahydro-2H-pyran-4-yl]methanol

Product 1

HCID 86721310N-{[(3S,4R,6R)-3-(5-bromo-2-fluorophenyl)-6-cyclopropyl-4-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]carbamothioyl}benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Benzoyl isothiocyanate (120 mg, 0.74 mmol) was added drop-wise to a solution of [(2R,4R,5S)-5-amino-5-(5-bromo-2-fluorophenyl)-2-cyclopropyltetrahydro-2H-pyran-4-yl]methanol (C56) (from the previous step, 225 mg, ≦0.78 mmol) in dichloromethane (25 mL) at 0° C. The reaction mixture was allowed to stir at 0° C. for 1.5 hours, then was warmed to room temperature and stirred overnight before concentrating in vacuo. Purification via silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) afforded the product as a solid. Yield: 127 mg, 26% over 2 steps LCMS m/z 454.3 [M+H+].

Workup

  1. temperaturewas warmed to room temperature
  2. stirringstirred overnight
  3. concentrationbefore concentrating in vacuo
  4. customPurification via silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-bed3177ca8254c78af6c88c1090e2c05
Source dataset
uspto-grants-2014_09
Patent number
US08822456B2

Reaction notes

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