Sodium hydride → HCID 178480093, compound

HRID 575669Notes

Reaction equation

HRID 575669 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([OH:8])[CH2:4][CH2:3]1.[H-].[Na+].F[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][C:13]=1[C:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25](=[O:32])[N:24]([CH3:33])[CH:23]=1>CN(C=O)C.O>[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([O:8][C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][C:13]=2[C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25](=[O:32])[N:24]([CH3:33])[CH:23]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 1180219014-(2-Fluoro-5-methylsulfonylphenyl)-2-methylisoquinolin-1-oneHCID 178511714HCID 178511714, compound

Product 1

HCID 178480093HCID 178480093, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To compound cis-4-aminocyclohexan-1-ol (275 mg, 1.81 mmol) in DMF (3 mL), was added NaH (127 mg, 3.17 mmol, 60% in mineral oil) in one portion at 0° C. The mixture was stirred at 0° C. for 30 min, 4-(2-fluoro-5-methylsulfonylphenyl)-2-methylisoquinolin-1-one (150.00 mg, 0.45 mmol) was added in one portion and the mixture stirred at 0° C. for 2 hrs. The reaction was diluted with water (20 mL) and extracted with EA (3×20 mL). The combined organic layers were washed with saturated brine (2×20 mL), dried with anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by prep-HPLC to give the title compound as its hydrochloride salt (91.01 mg, 47.1%). 1H NMR (DMSO-d6, 400 MHz) δ 8.29 (d, J=8.0 Hz, 1H), 8.00 (s, 3H), 7.95 (dd, J1=8.8 Hz, J2=2.0 Hz, 1H), 7.81 (d, J=2.0 Hz, 1H), 7.64 (t, J=7.2 Hz, 1H), 7.56 (s, 1H), 7.51 (t, J=7.2 Hz, 1H), 7.40 (d, J=8.8 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 4.70 (s, 1H), 3.59 (s, 3H), 3.22 (s, 3H), 2.96-2.94 (m, 1H), 1.85-1.82 (m, 1H), 1.64-1.46 (m, 5H), 1.32-1.26 (m, 1H), 1.04-0.98 (m, 1H). LCMS (M+H)+=427.0 (M+H)+

Workup

  1. stirringthe mixture stirred at 0° C. for 2 hrs
  2. extractionextracted with EA (3×20 mL)
  3. washThe combined organic layers were washed with saturated brine (2×20 mL)
  4. dry with materialdried with anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuum
  7. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-a48ca14b376a462986dc3d58f3eb8935
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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