Water → HCID 118116651, compound

HRID 1487344Notes

Reaction equation

HRID 1487344 reaction equation
[F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][S:12]([CH2:15][CH3:16])(=[O:14])=[O:13])=[CH:7][C:6]=1[C:17]1[C:22]([O:23][CH2:24][CH3:25])=[CH:21][C:20](=[O:26])[N:19]([CH3:27])[CH:18]=1.[H-].[Na+].Br[CH2:36][CH:37]1[CH2:39][CH2:38]1.O>CN(C=O)C>[CH:37]1([CH2:36][N:11]([C:8]2[CH:9]=[CH:10][C:5]([O:4][C:3]3[CH:28]=[CH:29][C:30]([F:32])=[CH:31][C:2]=3[F:1])=[C:6]([C:17]3[C:22]([O:23][CH2:24][CH3:25])=[CH:21][C:20](=[O:26])[N:19]([CH3:27])[CH:18]=3)[CH:7]=2)[S:12]([CH2:15][CH3:16])(=[O:13])=[O:14])[CH2:39][CH2:38]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 90018193HCID 90018193, compound

Product 1

HCID 118116651HCID 118116651, compoundYield 8.96%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Example 72A (50 mg, 0.108 mmol) in DMF (1 mL) was added NaH (7.7 mg, 0.32 mmol) and the mixture was stirred at room temperature for 30 minutes. Then (bromomethyl)cyclopropane (43.6 mg, 0.323 mmol) was added and the mixture was stirred at 50° C. for 18 hours. Water (10 mL) was added and the mixture extracted with ethyl acetate (3×15 mL). The combined organics were washed with brine, dried (MgSO4), filtered, and concentrated. The residue was purified by HPLC (C18, CH3CN/water (0.1% NH4HCO3), 40-60%) to provide the title compound (5 mg, 8.96% yield). 1H NMR (400 MHz, CD3OD) δ 7.46 (s, 1H), 7.28 (dd, J=6.9, 2.6 Hz, 2H), 6.92 (dd, J=12.2, 8.4 Hz, 2H), 6.80 (d, J=9.6 Hz, 2H), 5.81 (s, 1H), 3.87 (q, J=7.0 Hz, 2H), 3.43 (d, J=7.1 Hz, 2H), 3.38 (s, 3H), 3.00 (q, J=7.4 Hz, 2H), 1.22 (t, J=7.4 Hz, 3H), 1.14 (t, J=7.0 Hz, 3H), 0.81 (d, J=7.8 Hz, 1H), 0.33 (dd, J=8.0, 1.2 Hz, 2H), 0.01 (d, J=5.9 Hz, 2H). MS (ESI+) m/z 519.2 (M+H)+.

Workup

  1. stirringthe mixture was stirred at 50° C. for 18 hours
  2. extractionthe mixture extracted with ethyl acetate (3×15 mL)
  3. washThe combined organics were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by HPLC (C18, CH3CN/water (0.1% NH4HCO3), 40-60%)

Sources & evidence

ORD record
ord-b2a1aa5310c445f2a61b6c9e03f14a22
Source dataset
uspto-grants-2016_08
Patent number
US09428514B2

Reaction notes

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