Hydrochloric Acid → HCID 49764671, compound

HRID 1035290Notes

Reaction equation

HRID 1035290 reaction equation
N([O-])=O.[Na+].N[C:6]1[CH:7]=[CH:8][C:9]2[N:15]3[CH2:16][CH2:17][N:18]([CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:19][CH:14]3[CH2:13][NH:12][C:11](=[O:27])[C:10]=2[CH:28]=1.Cl>O.[PH2](O)=O>[CH2:20]([N:18]1[CH2:17][CH2:16][N:15]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:28][C:10]=3[C:11](=[O:27])[NH:12][CH2:13][CH:14]2[CH2:19]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 23668193Sodium NitriteHCID 667702009-Amino-3-benzyl-2,3,4,4a,5,6-hexahydrobenzo[f]pyrazino[1,2-a][1,4]diazepin-7(1h)-one

Product 1

HCID 49764671HCID 49764671, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 4124402Phosphinic AcidSolvent

Procedure

A solution of sodium nitrite (0.033 g, 0.478 mmol) in water (2.171 mL) was added to an ice bath chilled solution of Example 45H (0.14 g, 0.434 mmol) in hypophosphorous acid, solution in water (9.03 mL, 87 mmol, 9.63 M) and HCl (2.140 mL, 26.1 mmol, 12.2 M). A sample was taken out after 10 minutes, quenched with 1 M NaOH (aqueous), and the reaction was determined to be complete by LC/MS. The reaction mixture was allowed to reach room temperature and was poured into 100 mL 1 M NaOH (aqueous). Additional 1 M NaOH (aqueous) was added until the pH=14. The product was extracted with dichloromethane three times, dried over sodium sulfate, and the solvent was evaporated. The residue was then purified by reverse phase HPLC to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.03 (s, 1H), 8.19 (t, J=5.8, 1H), 7.61-7.50 (m, 5H), 7.50-7.39 (m, 2H), 7.11 (t, J=7.3, 1H), 7.04 (d, J=7.9, 1H), 4.47 (s, 2H), 3.37-3.10 (m, 6H), 3.02 (dd, J=6.5, 14.9, 1H); MS (ESI+) m/z 308.0 (M+H)+.

Workup

  1. customquenched with 1 M NaOH (aqueous)
  2. customto reach room temperature
  3. additionwas poured into 100 mL 1 M NaOH (aqueous)
  4. additionAdditional 1 M NaOH (aqueous) was added until the pH=14
  5. extractionThe product was extracted with dichloromethane three times
  6. dry with materialdried over sodium sulfate
  7. customthe solvent was evaporated
  8. customThe residue was then purified by reverse phase HPLC

Sources & evidence

ORD record
ord-cbfd1625429548f985e929e389c8e2ed
Source dataset
uspto-grants-2013_10
Patent number
US08546377B2

Reaction notes

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