Sodium Carbonate → HCID 70195144, compound

HRID 2393286Notes

Reaction equation

HRID 2393286 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[F:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[C@@:15]([OH:42])([CH2:36][N:37]1[CH:41]=[N:40][CH:39]=[N:38]1)[C@H:16]([N:18]1[C:23](=[O:24])[C:22]2[S:25][C:26]([C:28]3[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=3)=[CH:27][C:21]=2[N:20]=[CH:19]1)[CH3:17].Cl.[NH2:44][OH:45]>O.C1COCC1>[F:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[C@@:15]([OH:42])([CH2:36][N:37]1[CH:41]=[N:40][CH:39]=[N:38]1)[C@H:16]([N:18]1[C:23](=[O:24])[C:22]2[S:25][C:26]([C:28]3[CH:35]=[CH:34][C:31]([CH:32]=[N:33][NH:44][OH:45])=[CH:30][CH:29]=3)=[CH:27][C:21]=2[N:20]=[CH:19]1)[CH3:17]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 443297Hydroxyamine hydrochlorideHCID 480234HCID 480234, compound

Product 1

HCID 70195144HCID 70195144, compoundYield 61.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Na2CO3 (0.84 g, 7.92 mmol) in a mixture of H2O (8 mL) and THF (30 mL) was added (1R,2R)-4-[3-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-6-yl]benzonitrile (0.5 g, 0.99 mmol, obtained in example 32) and hydroxylamine hydrochloride (0.35 g, 1.95 mmol). The mixture was stirred at reflux overnight, concentrated and the aqueous residue was extracted with CHCl3. The organic phase was separated, dried over Na2SO4, filtered and the filtrate concentrated to a solid which was purified by flash chromatography to give the title compound as a pale yellow solid (325 mg, 61%): mp 246°-247° C.; 1H NMR (300 MHz, MeOH-d4) δ (MeOH) 8.60 (s, 1H, N=CH--N), 8.18 (s, 1H, triazole), 7.86 (d, J=8.5, 2H, arom), 7.78 (d, J=8.5, 2H, arom), 7.71 (s, 1H, triazole), 7.66 (s, 1H, thiophene), 7.43 (dt, Jt =6.5, Jd =9, 1H, arom), 7.06 (ddd, Jd =2.5, Jd =8.5, Jd =14, 1H, arom), 6.89 (dt, Jd =2.5, Jt =8.5, 1H, arom), 6.09 (q, J=7.3, 1H, MeCH), 5.09 (d, J=14.2, 1H, CH(H)), 4.19 (d, J=14.2, 1H, CH(H)), 1.32 (d, J=7.3, 3H, CHMe); MS 314 (N-ethylheterocycle, C15H14N4O2S), 224 (Tr--CH2COHAr, C10H8F2N3O); [α]D =+74.9° (c 1, MeOH). Analysis calculated for C25H21F2N7O3S: C 55.86; H 3.94; N 18.24; S 5.96. Found: C 55.10; H 3.84; N 17.72; S 5.69.

Workup

  1. temperatureat reflux overnight
  2. concentrationconcentrated
  3. extractionthe aqueous residue was extracted with CHCl3
  4. customThe organic phase was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated to a solid which
  8. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-3a7ff678d0b446f4ae2261d03a900c0a
Source dataset
uspto-grants-1998_09
Patent number
US05807854

Reaction notes

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