Dichloromethane → 7-Bromo-2,9-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole

HRID 930636Notes

Reaction equation

HRID 930636 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[CH2:15][CH2:14][NH:13][CH2:12][C:7]=3[N:8]2[CH3:11])=[CH:4][CH:3]=1.[BH-](OC(C)=O)(OC(C)=O)O[C:18](C)=O.[Na+].C(Cl)[Cl:31]>CO.C=O>[Cl-:31].[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[CH2:15][CH2:14][N:13]([CH3:18])[CH2:12][C:7]=3[N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 6344Dichloromethane2×HCID 5049666Sodium triacetoxyborohydrideHCID 579503917-Bromo-9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole

Product 2

HCID 312ChlorideHCID 579503597-Bromo-2,9-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoleYield 88%

Reagents, catalysts & solvents 2

HCID 712FormaldehydeSolventHCID 887MethanolSolvent

Procedure

7-Bromo-9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (1.24 g, 4.68 mmol) was dissolved in a mixture of MeOH (20 mL) and CH2Cl2 (5 mL) and formaldehyde (0.56 mL, 37% aqueous solution) was added. After stirring for 1 h, NaBH(OAc)3 (1.98 g, 9.34 mmol) was added and the mixture stirred for a further 10 minutes. The mixture was diluted with methylene chloride (50 mL), washed with saturated Na2CO3 solution, concentrated and purified by flash column chromatography (40 g ISCO column eluting with methylene chloride and a methanol/ammonia mixture (10:1); gradient (s, 2H), ylene chloride to 90% methylene chloride over 30 min at 40 mL/min) to provide the title compound (1.15 g, 88%) as a white powder: 1H NMR (500 MHz, CDCl3) δ 7.40 (d, J=1.6 Hz, 1H), 7.32 (d, J=8.4 Hz, 1H), 7.16 (dd, J=8.3, 1.7 Hz, 1H), 3.61 (s, 2H), 3.55 (s, 3H), 2.86-2.76 (m, 4H), 2.56 (s, 3H).

Workup

  1. additionwas added
  2. stirringthe mixture stirred for a further 10 minutes
  3. washwashed with saturated Na2CO3 solution
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (40 g ISCO column
  6. washeluting with methylene chloride

Sources & evidence

ORD record
ord-7a7196487bcc457c99899f1caeab1e64
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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