Hydrochloric Acid → HCID 86696693, compound

HRID 2365838Notes

Reaction equation

HRID 2365838 reaction equation
Cl.O1CCOCC1.[Si]([O:15][CH2:16][C@@H:17]([N:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C@H:38]3[CH2:43][CH2:42][O:41][CH2:40][C@H:39]3[F:44])[N:32]=2)=[CH:27][C:26]1=[O:45])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=1)(C(C)(C)C)(C)C>CO>[Cl:24][C:20]1[CH:19]=[C:18]([C@H:17]([N:25]2[CH:30]=[CH:29][C:28]([C:31]3[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C@H:38]4[CH2:43][CH2:42][O:41][CH2:40][C@H:39]4[F:44])[N:32]=3)=[CH:27][C:26]2=[O:45])[CH2:16][OH:15])[CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86696694HCID 86696694, compound

Product 1

HCID 86696693HCID 86696693, compoundYield 95.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4M HCl in dioxane (0.939 mL, 3.76 mmol) was added to 1-((S)-2-(tert-butyldimethylsilyloxy)-1-(3-chlorophenyl)ethyl)-4-(2-(((3S,4S)-3-fluorotetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (0.105 g, 0.188 mmol) in MeOH (5 mL). After 30 minutes, the reaction mixture was evaporated, and the residue was partitioned between EtOAc and saturated aqueous NaHCO3. The EtOAc was washed with brine, dried over MgSO4, filtered, and evaporated to yield a crude product (0.08 g) as a film. This was chromatographed on a 10 g Biotage SNAP column with 10:1 EtOAc/1-PrOH. Fractions 9-16 contained 1-((S)-1-(3-chlorophenyl)-2-hydroxyethyl)-4-(2-(((3S,4S)-3-fluorotetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one as a solid foam. 1H NMR (400 MHz, CD3OD) δ 8.38 (d, 1H), 7.80 (d, 1H), 7.41-7.39 (m, 1H), 7.38-7.28 (m, 2H), 7.22 (d, 1H), 7.09 (d, 1H), 7.00-6.97 (m, 1H), 6.15-6.11 (m, 1H), 4.83-4.70 (m, 1H), 4.34-4.25 (m, 2H), 4.20-4.15 (m, 1H), 4.01-3.98 (m, 1H), 3.94-3.88 (m, 1H), 3.70-3.54 (m, 2H), 2.08-1.95 (m, 1H), 1.83-1.77 (m, 1H) 1.13 (d, 1H); m/z (APCI-pos) M+1=445.1; 97.5% e.e. by chiral HPLC (Chiral Tech, column OD-H, 4.6 mm×250 mm, 5 u, 20% ethanol/80% hexanes, 1 mL/minute).

Workup

  1. customthe reaction mixture was evaporated
  2. customthe residue was partitioned between EtOAc and saturated aqueous NaHCO3
  3. washThe EtOAc was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-ef64a84db23a4854a0f6c484ef8f9013
Source dataset
uspto-grants-2014_04
Patent number
US08697715B2

Reaction notes

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