Sodium hydride → HCID 68733724, compound

HRID 1523245Notes

Reaction equation

HRID 1523245 reaction equation
[H-].[Na+].[NH2:3][C@@:4]([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)([CH2:21][CH:22]=[CH2:23])[CH2:5][CH2:6][N:7]([C@H:12]([C:14]1[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][CH:15]=1)[CH3:13])[C:8](=O)[O:9]C>C1COCC1.C(Cl)Cl>[CH2:21]([C:4]1([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[CH2:5][CH2:6][N:7]([C@H:12]([C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][CH:15]=2)[CH3:13])[C:8](=[O:9])[NH:3]1)[CH:22]=[CH2:23]

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 59627206HCID 59627206, compound

Product 1

HCID 68733724HCID 68733724, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of NaH (100 mg, 4 mmol) and anhydrous THF (8 mL) was added dropwise a solution of crude methyl (S)-3-amino-3-(4-fluorophenyl)hex-5-enyl((S)-1-(4-bromophenyl)ethyl)carbamate (39 mg, 0.1 mmol) in anhydrous THF (8 mL) at 0° C. The reaction mixture was refluxed overnight. The reaction mixture was quenched with methanol in an ice bath and evaporated to leave a residue, which was dissolved in CH2Cl2. The combined organic phase was dried, filtered and concentrated to give the crude product, which was purified by TLC to provide (S)-4-allyl-1-((S)-1-(4-bromophenyl)ethyl)-4-(4-fluorophenyptetrahydropyrimidin-2(1H)-one (1.2 mg, 3%). LC-MS Method 1 tR=1.603 min, m/z=419; 1H NMR (CD3OD) 1.36 (d, 3H), 1.81-1.92 (m, 1H), 2.16-2.22 (m, 1H), 2.46-2.53 (m, 1H), 2.61-2.84 (m, 3H), 5.12-5.19 (m, 1H), 5.56-5.69 (m, 1H), 7.06-7.13 (m, 2H), 7.18-7.24 (m, 2H), 7.22-7.29 (m, 2H), 7.42-7.51 (m, 2H).

Workup

  1. temperatureThe reaction mixture was refluxed overnight
  2. customThe reaction mixture was quenched with methanol in an ice bath
  3. customevaporated
  4. customto leave a residue, which
  5. customThe combined organic phase was dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas purified by TLC
  10. customto provide (S)-4-allyl-1-((S)-1-(4-bromophenyl)ethyl)-4-(4-fluorophenyptetrahydropyrimidin-2(1H)-one (1.2 mg, 3%)

Sources & evidence

ORD record
ord-a9db6c4fd59043b8837ff6fc28d2cde0
Source dataset
uspto-grants-2015_07
Patent number
US09079861B2

Reaction notes

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