Acetone → HCID 11681450, compound

HRID 2100618Notes

Reaction equation

HRID 2100618 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.[CH3:19][C:20]([CH3:22])=O.[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]([CH:20]([CH3:22])[CH3:19])[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 180AcetoneHCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 11716184HCID 11716184, compound

Product 1

HCID 11681450HCID 11681450, compoundYield 119.6%

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) (19 mg, 0.066 mmol) in 2 mL of methanol was added acetone (0.015 mL, 0.20 mmol) followed by sodium borohydride (13 mg, 0.33 mmol) portionwise. 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 13 mg (60%) of the title compound of Example 64 as a white solid. 1H NMR (CD3OD): 7.36 (s, 1H), 7.07 and 7.02 (s, 1H), 4.27-4.21 and 4.16-4.11 (m, 1H), 3.88-3.35 (overlapping m, 6H), 2.70 (q, 2H), 1.48-1.42 (m, 6H), 1.26 (t, 3H). LRMS (ESI): 293.3/295.3 (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-cdddde4740304959b882034e04beea57
Source dataset
uspto-grants-2009_08
Patent number
US07572805B2

Reaction notes

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