Ammonium Hydroxide → HCID 5481912, compound

HRID 1419700Notes

Reaction equation

HRID 1419700 reaction equation
[NH4+].[OH-].CS(O)(=O)=[O:5].[C:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16]2[S:17][C:18]([C:22]([NH:24][C@H:25]([CH3:42])[C@:26]([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][C:35]=3[F:41])([OH:33])[CH2:27][N:28]3[CH:32]=[N:31][CH:30]=[N:29]3)=[O:23])=[C:19]([CH3:21])[N:20]=2)=[CH:12][CH:11]=1)#[N:9]>>[C:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16]2[S:17][C:18]([C:22]([NH:24][C@H:25]([CH3:42])[C@:26]([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][C:35]=3[F:41])([OH:33])[CH2:27][N:28]3[CH:32]=[N:31][CH:30]=[N:29]3)=[O:23])=[C:19]([CH3:21])[N:20]=2)=[CH:12][CH:11]=1)(=[O:5])[NH2:9]

Participants

3

Reactant 2

HCID 14923Ammonium HydroxideHCID 10031340HCID 10031340, compound

Product 1

HCID 5481912HCID 5481912, compound

Procedure

To a solution of NH4OH in a H2O--THF mixture was added (1R,2R)-2-(4-cyanophenyl)-N-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-methyl thiazole-5-carboxamide methanesulfonate (0.5 g, 0.84 mmol, obtained in example 31). The mixture was refluxed for 2 days, then was concentrated and the aqueous residue was extracted with CHCl3. The organic layer was separated, dried over Na2SO4, filtered and the filtrate was concentrated to a solid (0.53 g). This was purified by flash chromatography to give the title compound as a white solid: 133°-135° C.; 1H NMR (300 MHz, CDCl3) δ (TMS) 7.98 (d, J=8.3, 2H, arom), 7.87 (d, J=8.3, 2H, arom), 7.81 (s, 1H, triazole), 7.71 (s, 1H, triazole), 7.40 (dt, Jd =6.5, Jt =8.8, 1H, arom), 6.8-6.6 (m, 2H, ) arom), 6.57 (br d, J=9.5, 1H, NH), 6.27 (br s, 2H, NH2), 5.63 (s, 1H, OH), 5.05 (d, J=14.5, 1H, TrCH(H)), 4.98 (br quint, J=7, 1H, CHMe), 4.57 (d, J=14.5, 1H, TrCH(H)), 2.81 (s, 3H, Me-thiazole), 1.05 (d, J=6.8, 3H, MeCH); MS 288 and 289 (ethylaminoacyl group, C14H15N3O2S), 245 (acyl group, C12H9N2O2S), 224 (Tr--CH2COHAr, C10H8F2N3O); [α]D =-74.5° (c 1, MeOH). Analysis calculated for C24H22F2N6O3S: C 56.24; H 4.33; N 16.40; S 6.26. Found: C 55.90; H 4.64; N 15.29; S 5.62.

Workup

  1. temperatureThe mixture was refluxed for 2 days
  2. concentrationwas concentrated
  3. extractionthe aqueous residue was extracted with CHCl3
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated to a solid (0.53 g)
  8. customThis was purified by flash chromatography

Sources & evidence

ORD record
ord-24782a48dab04480b573654c14a4ed7b
Source dataset
uspto-grants-1999_03
Patent number
US05888941

Reaction notes

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