Acetaldehyde → HCID 11580484, compound

HRID 2100619Notes

Reaction equation

HRID 2100619 reaction equation
Cl.[Cl:2][C:3]1[C:12]2[C:11](=[O:13])[NH:10][C@H:9]3[CH2:14][NH:15][CH2:16][C@@H:8]3[C:7]=2[CH:6]=[C:5]([CH2:17][CH3:18])[CH:4]=1.[CH:19](=O)[CH3:20].[BH4-].[Na+].Cl>CO.CCOCC.O1CCOCC1>[ClH:2].[Cl:2][C:3]1[C:12]2[C:11](=[O:13])[NH:10][C@H:9]3[CH2:14][N:15]([CH2:19][CH3:20])[CH2:16][C@@H:8]3[C:7]=2[CH:6]=[C:5]([CH2:17][CH3:18])[CH:4]=1

Participants

8

Reactant 4

HCID 177AcetaldehydeHCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 11716184HCID 11716184, compound

Product 1

HCID 11580484HCID 11580484, compoundYield 126.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (3aR,9bS)-6-chloro-8-ethyl-2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-one hydrochloride (Example 29) (10 mg, 0.035 mmol) in 2 mL of methanol was added acetaldehyde (0.006 mL, 0.10 mmol) followed by sodium borohydride (7 mg, 0.17 mmol). The reaction mixture was stirred at ambient temperature for 18 h. The reaction was concentrated and the residue was purified (ISCO, elution with 0-15% methanol/methylene chloride) to afford the free base. To the free base in 1 mL of ether was added 4N HCl in dioxane (0.05 mL). The mixture was concentrated in vacuo, triturated with ether, and dried in vacuo to afford 7 mg (64%) of the title compound of Example 65 as an off-white solid. 1H NMR (CD3OD): 7.27 (s, 1H), 6.95 and 6.91 (s, 1H), 4.30-4.25 and 3.93-3.85 (m, 2H), 3.70-52 (overlapping m, 3H), 3.42-3.27 (overlapping m, 3H), 2.61 (q, 2H), 1.33 (q, 3H), 1.16 (t, 3H). LRMS (ESI): 279.2/281.2 (M+H)+.

Workup

  1. concentrationThe reaction was concentrated
  2. customthe residue was purified
  3. wash(ISCO, elution with 0-15% methanol/methylene chloride)
  4. customto afford the free base
  5. concentrationThe mixture was concentrated in vacuo
  6. customtriturated with ether
  7. customdried in vacuo

Sources & evidence

ORD record
ord-bf96f725c7264329acb48c7a5ebe7ee1
Source dataset
uspto-grants-2009_08
Patent number
US07572805B2

Reaction notes

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