Hydrochloric Acid → HCID 131724554, compound

HRID 1836599Notes

Reaction equation

HRID 1836599 reaction equation
[CH:1]1[C:16]2=[C:17]3[C:4]([CH2:5][CH2:6][CH2:7][N:8]3[CH2:9][C@@H:10]3[C@H:15]2[CH2:14][NH:13][CH2:12][CH2:11]3)=[CH:3][CH:2]=1.C=O.[C:20](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[ClH:34]>ClCCCl.C(O)C.CCOCC.C(O)(=O)C>[ClH:34].[ClH:34].[CH3:20][N:13]1[CH2:12][CH2:11][C@H:10]2[C@H:15]([C:16]3[CH:1]=[CH:2][CH:3]=[C:4]4[C:17]=3[N:8]([CH2:7][CH2:6][CH2:5]4)[CH2:9]2)[CH2:14]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 60088320HCID 60088320, compound

Product 1

HCID 131724554HCID 131724554, compound

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of (±)-cis 5,6,8a,9,10,11,12,12a-octahydro-4H,8H-quino[1,8-bc]-2,6-naphthyridine free base from EXAMPLE 123 (50 mg, 0.22 mmol) in 10 mL of 1,2-dichloroethane was added 37% aqueous formaldehyde (0.05 mL, 0.58 mmol) and sodium triacetoxyborohydride (0.19 g, 0.87 mmol) and a couple drops of acetic acid. 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 (40 mg, 0.16 mmol) was dissolved in 1 mL ethanol and 5 mL of ether and then there was added 2M HCl in ether (0.25 mL, 0.5 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 the title compound of EXAMPLE 125 as an off white powder. 1H NMR (dmso-D6) δ: 10.65 (broad s, 1H), 6.77 (d, 1H, J=7.0 Hz), 6.73 (d, 1H, J=7.7 Hz), 6.47 (t, 1H, J=7.4 Hz), 3.45-3.35 (m, 1H), 3.30-2.85 (overlapping m, 8H), 2.80-2.58 (m, 8H), 2.35-2.25 (m, 1H), 2.22-2.15 (m, 1H), 1.90-1.75 (m, 3H). LRMS (ES)+: 243.4 (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. customA solid precipitated out of solution
  7. customThe solvents were decanted
  8. customthe solid was triturated twice with ether
  9. customdried in vacuo

Sources & evidence

ORD record
ord-e366673e9cea4f36b7c08ae9fc1d2682
Source dataset
uspto-grants-2004_08
Patent number
US06777406B2

Reaction notes

Loading…