Hydrochloric Acid → HCID 131724534, compound

HRID 1836567Notes

Reaction equation

HRID 1836567 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]3[C:14]4=[C:15]([CH2:17][CH2:18][CH2:19][N:13]4[CH2:12][C@@H:11]4[CH2:20][NH:21][CH2:22][C@H:10]34)[CH:16]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:23].Cl.[C:25]1(C2C=C3C4=C(CCCN4C[C@@H]4CNC[C@H]34)C=2)C=CC=CC=1.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCCl.C(O)(=O)C.CCOCC>[ClH:23].[ClH:23].[CH3:25][N:21]1[CH2:22][C@H:10]2[C@H:11]([CH2:12][N:13]3[CH2:19][CH2:18][CH2:17][C:15]4[CH:16]=[C:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[CH:8]=[C:9]2[C:14]3=4)[CH2:20]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 23518405HCID 23518405, compoundHCID 69917388HCID 69917388, compound

Product 1

HCID 131724534HCID 131724534, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 111,2-DichloroethaneSolventHCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of (±)-cis-2-phenyl-5,6,8,8a,9,10,11,11a-octahydro-4H-pyrido[3,2,1-ij]pyrrolo[3,4-c]quinoline, the free base of EXAMPLE 15, (20 mg, 0.07 mmol) in 2 mL of 1,2-dichloroethane was added 37% aqueous formaldehyde (0.010 mL, 0.11 mmol), sodium triacetoxyborohydride (37 mg, 0.17 mmol) and glacial acetic acid (1 drop). The resulting mixture was stirred at ambient temperature for 1 h and then the reaction was quenched with water. The mixture was partitioned between chloroform and saturated aqueous sodium carbonate. The organics were washed with brine, dried (K2CO3) and concentrated in vacuo. The residue was dissolved in 1 mL ethanol and 5 mL of ether and then there was added 2M HCl in ether (0.07 mL, 0.14 mmol). A solid precipitated out of solution. The solvents were decanted and the solid was triturated twice with ether and dried in vacuo to afford 20 mg (77%) of the title compound of EXAMPLE 16 as an off white powder. 1H NMR (d6-dmso): δ 7.55-7.50 (m, 2H), 71.35 (app t, 2H, J=7.5 Hz), 7.24-7.17 (m, 2H), 7.14 (s, 1H), 4.07-3.98 (m, 1H), 3.82-3.73 (m, 1H), 3.44-3.32 (m, 1H), 3.10-3.03 (m, 2H), 3.02-2.97 (m, 1H), 2.94-2.70 (m, 9H), 1.97-1.85 (m, 2H). LRMS (ES)+: 305.3 (M+H)+.

Workup

  1. customthe reaction was quenched with water
  2. customThe mixture was partitioned between chloroform and saturated aqueous sodium carbonate
  3. washThe organics were washed with brine
  4. dry with materialdried (K2CO3)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in 1 mL ethanol
  7. customA solid precipitated out of solution
  8. customThe solvents were decanted
  9. customthe solid was triturated twice with ether
  10. customdried in vacuo

Sources & evidence

ORD record
ord-8da8ce11116a4aa1b4de494e662ba868
Source dataset
uspto-grants-2004_08
Patent number
US06777406B2

Reaction notes

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