Sodium hydride → HCID 90387231, compound

HRID 1476862Notes

Reaction equation

HRID 1476862 reaction equation
[OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[H-].[Na+].Cl[C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([F:27])[CH:25]=2)[CH:20]=[C:19]([Cl:28])[N:18]=1>C1COCC1.CCOC(C)=O>[Cl:28][C:19]1[N:18]=[C:17]([O:1][C@H:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]2)[C:26]2[C:21]([CH:20]=1)=[CH:22][CH:23]=[C:24]([F:27])[CH:25]=2

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 854055tert-Butyl (3S)-3-hydroxypyrrolidine-1-carboxylateHCID 269860371,3-Dichloro-7-fluoroisoquinoline

Product 1

HCID 90387231HCID 90387231, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate (1.56 g, 8.3 mmol) in THF (20 mL) was added NaH (0.33 g, 8.3 mmol) under nitrogen at 0° C. The mixture was warmed to RT over a 30 minute period and 1,3-dichloro-7-fluoroisoquinoline (0.9 g, 4.17 mmol) was added. The resulting mixture was stirred for 10 hours at RT. The mixture was subsequently diluted with EtOAc (100 mL), quenched with saturated aqueous NH4Cl (100 mL), and extracted with EtOAc (3×100 mL). The combined organic layers were dried over Na2SO4 and concentrated. The crude product was purified by column chromatography eluting with petroleum ether and ethyl acetate (PE/EtOAc=50:1-10:1 gradient) to give the title compound (1.1 g, 72%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.00-7.98 (m, 1H), 7.82-7.80 (m, 2H), 7.62 (s, 1H), 5.67-5.63 (d, J=16 Hz, 1H), 3.69-3.66 (m, 1H), 3.53-3.487 (m, 3H), 2.30-2.22 (m, 2H), 1.41-1.39 (d, J=10.8 Hz, 2H).

Workup

  1. customquenched with saturated aqueous NH4Cl (100 mL)
  2. extractionextracted with EtOAc (3×100 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography
  6. washeluting with petroleum ether and ethyl acetate (PE/EtOAc=50:1-10:1 gradient)

Sources & evidence

ORD record
ord-0768e1f84c3540bea12e88ba713ab40e
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

Loading…