Hydrochloric Acid → HCID 57947853, compound

HRID 409870Notes

Reaction equation

HRID 409870 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([NH:12][C:13](=[O:39])[O:14][CH2:15][C@@H:16]([N:25]([CH3:38])[C:26]([NH:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:31]=1[Cl:37])=[O:27])[CH2:17][C:18]([F:24])([F:23])[CH2:19][N:20]=[N+]=[N-])=[CH:5]2.C1COCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>O>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([NH:12][C:13](=[O:39])[O:14][CH2:15][C@@H:16]([N:25]([CH3:38])[C:26]([NH:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:31]=1[Cl:37])=[O:27])[CH2:17][C:18]([F:23])([F:24])[CH2:19][NH2:20])=[CH:5]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 57947867HCID 57947867, compound

Product 1

HCID 57947853HCID 57947853, compoundYield 50.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of (S)-5-azido-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4,4-difluoropentyl 6-fluoroisoquinolin-3-ylcarbamate (25.0 g, 0.0441 mol), THF (300 mL) and water (100 mL) was added triphenylphosphine (13.9 g, 0.0529 mol) and aq. HCl solution (53 mL, 2N, 0.106 mol). The resulting mixture was stirred at RT for 1 h and concentrated down to about 200 mL. Water (200 mL) was then added. The resulting mixture (pH<4) was extracted with EtOAc (300 mL) and the EtOAc solution was discarded. The remaining aq. solution was adjusted to pH>8 by adding NaOH (2N) and extracted with DCM (200 mL×3). The organic layer was washed with water and brine, dried over Na2SO4. The organic layers were combined and concentrated. The resulting residue was purified on silica gel column (DCM/MeOH) to give (S)-5-amino-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4,4-difluoropentyl 6-fluoroisoquinolin-3-ylcarbamate (12.1 g, 50.7%). LRMS (M+H+) m/z 542.5.

Workup

  1. concentrationconcentrated down to about 200 mL
  2. additionWater (200 mL) was then added
  3. extractionThe resulting mixture (pH<4) was extracted with EtOAc (300 mL)
  4. additionby adding NaOH (2N)
  5. extractionextracted with DCM (200 mL×3)
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe resulting residue was purified on silica gel column (DCM/MeOH)

Sources & evidence

ORD record
ord-8da30a84567b45789bf95a23e41153c6
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Reaction notes

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