Ammonium Chloride → 10-Hydroxy-10-(3-methoxy-2-methylpropyl)-2,3,4,10-tetrahydropyrimido[1,2-a]indole

HRID 2231821Notes

Reaction equation

HRID 2231821 reaction equation
Br[CH2:2][CH:3]([CH3:7])[CH2:4][O:5][CH3:6].[Mg].[N:9]1[CH2:10][CH2:11][CH2:12][N:13]2[C:21]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[C:15](=[O:22])[C:14]=12.[Cl-].[NH4+]>CCOCC.ClCCCl>[OH:22][C:15]1([CH2:2][CH:3]([CH3:7])[CH2:4][O:5][CH3:6])[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=2[N:13]2[CH2:12][CH2:11][CH2:10][N:9]=[C:14]12

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 141813833,4-Dihydropyrimido(1,2-a)indol-10(2h)-oneHCID 212848141-Bromo-3-methoxy-2-methylpropane

Product 1

HCID 1418140110-Hydroxy-10-(3-methoxy-2-methylpropyl)-2,3,4,10-tetrahydropyrimido[1,2-a]indole

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 3283Diethyl EtherSolvent2×

Procedure

1-Bromo-3-methoxy-2-methylpropane (10.02 g) in ether (50 ml) was added dropwise over 20 minutes to magnesium turnings (1.46 g) in ether (10 ml). The mixture was stirred under argon at room temperature for 30 minutes, cooled to 0° and 3,4-dihydropyrimido[1,2-a]indol-10(2H)-one (3.72 g) in dry 1,2-dichloroethane (20 ml) added dropwise over 20 minutes. The solution was stirred under argon at 0° for 1 hour, poured onto a swirling mixture of ice (100 ml) and saturated aqueous ammonium chloride (60 ml). The mixture was stirred for 20 minutes and concentrated in vacuo. The aqueous residue was extracted with chloroform (3×100 ml). The extracts were dried (Na2SO4) and concentrated in vacuo. Ether (20 ml) was added and the product was filtered and recrystallised from ethyl acetate to give the title compound as the free base (2.85 g), m.p. 162°-167° C. The free base was acidified with ethereal HCl to give the title compound as the hydrochloride, m.p. 244° (dec.).

Workup

  1. temperaturecooled to 0°
  2. stirringThe solution was stirred under argon at 0° for 1 hour
  3. stirringThe mixture was stirred for 20 minutes
  4. concentrationconcentrated in vacuo
  5. extractionThe aqueous residue was extracted with chloroform (3×100 ml)
  6. dry with materialThe extracts were dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. additionEther (20 ml) was added
  9. filtrationthe product was filtered
  10. customrecrystallised from ethyl acetate

Sources & evidence

ORD record
ord-b7217d2fe0cb451b86ef71bc27825076
Source dataset
uspto-grants-1988_11
Patent number
US04784996

Reaction notes

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