Propargyl bromide → HCID 90454530, compound

HRID 530831Notes

Reaction equation

HRID 530831 reaction equation
[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][NH:8][C:9]2[C:10](=[O:29])[N:11]([CH3:28])[N:12]=[C:13]([O:15][CH2:16][C@H:17]3[CH2:19][C@@H:18]3[C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][N:21]=3)[CH:14]=2)=[CH:5][CH:4]=1.[H-].[Na+].Br[CH2:35][C:36]#[CH:37]>C1COCC1.O.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]([CH2:37][C:36]#[CH:35])[C:9]2[C:10](=[O:29])[N:11]([CH3:28])[N:12]=[C:13]([O:15][CH2:16][C@H:17]3[CH2:19][C@@H:18]3[C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][N:21]=3)[CH:14]=2)=[CH:30][CH:31]=1

Participants

7

Reactant 3

HCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 90454533HCID 90454533, compound

Product 1

HCID 90454530HCID 90454530, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(4-methoxybenzylamino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one (210 mg, 0.50 mmol) in THF (20 mL) was added NaH (30 mg, 0.75 mmol) at 0° C. After stirred for 10 min, 3-bromoprop-1-yne (118 mg, 1.00 mmol) was added. The mixture was stirred for 2 h at room temperature and then diluted with H2O (20 mL) and EtOAc (50 mL). The organic phase was washed with H2O and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel, eluting with PE/EA (4/1) to give the title compound as oil. ESI-MS: 461.2 (M+H)+. 1H NMR (400 MHz, MeOD) δ 7.95 (d, 1H), 7.21-7.18 (m, 3H), 7.07 (d, 1H), 6.78 (d, 2H), 6.19 (s, 1H), 4.50 (s, 2H), 4.10-3.94 (m, 4H), 3.75 (s, 3H), 3.74 (s, 3H), 3.72 (s, 3H), 2.61 (s, 1H), 2.00-1.96 (m, 1H), 1.68-1.63 (m, 1H), 1.11-1.00 (m, 1H), 0.95-0.97 (m, 1H).

Workup

  1. stirringThe mixture was stirred for 2 h at room temperature
  2. washThe organic phase was washed with H2O and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel
  7. washeluting with PE/EA (4/1)

Sources & evidence

ORD record
ord-6ba7fa5d103442ac8ce9bfceced39b44
Source dataset
uspto-grants-2016_05
Patent number
US09353104B2

Reaction notes

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