Formaldehyde → HCID 11695131, compound

HRID 2100617Notes

Reaction equation

HRID 2100617 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.[CH2:19]=O.[BH4-].[Na+]>CO.CCOCC.Cl>[ClH:2].[Cl:2][C:3]1[C:12]2[C:11](=[O:13])[NH:10][C@H:9]3[CH2:14][N:15]([CH3:19])[CH2:16][C@@H:8]3[C:7]=2[CH:6]=[C:5]([CH2:17][CH3:18])[CH:4]=1

Participants

7

Reactant 3

HCID 712FormaldehydeHCID 4311764Sodium borohydrideHCID 11716184HCID 11716184, compound

Product 1

HCID 11695131HCID 11695131, compoundYield 142.3%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

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) (20 mg, 0.07 mmol) in 2 mL of methanol was added formaldehyde (0.017 mL of 37% aqueous solution, 0.21 mmol) followed by sodium borohydride (14 mg, 0.35 mmol) portionwise. The reaction mixture was stirred at ambient temperature for 1 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 two drops 12 N HCl. The mixture was concentrated in vacuo, triturated with ether, and dried in vacuo to afford 15 mg (71%) of the title compound of Example 62 as an off-white solid. 1H NMR (CD3OD): 7.35 (s, 1H), 7.00 and 6.97 (s, 1H), 4.07-4.02 (m, 1H), 3.91-3.85 (m, 1H), 3.74-3.69 (m, 1H), 3.61-3.55 (m, 1H), 3.45-3.28 (m, 2H), 3.14 and 3.08 (s, 3H), 2.69 (q, 2H), 1.25 (t, 3H). LRMS (ESI): 265.2/267.2 (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-9790fbdb74bc41ee9014ae46bf760a18
Source dataset
uspto-grants-2009_08
Patent number
US07572805B2

Reaction notes

Loading…