Sodium Bicarbonate → N-(6-chloro-7-methylsulfanyl-9H-beta-carbolin-8-yl)-2-methyl-nicotinamide

HRID 552201Notes

Reaction equation

HRID 552201 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH2:17])[C:14]=1[S:15][CH3:16])[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1.[CH3:18][C:19]1[N:27]=[CH:26][CH:25]=[CH:24][C:20]=1[C:21](O)=[O:22].Cl.CN(C)CCCN=C=NCC.C(=O)(O)[O-].[Na+]>N1C=CC=CC=1.CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH:17][C:21](=[O:22])[C:20]3[CH:24]=[CH:25][CH:26]=[N:27][C:19]=3[CH3:18])[C:14]=1[S:15][CH3:16])[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 6433732-Methylnicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 671666356-chloro-7-methylsulfanyl-9H-beta-carbolin-8-ylamine2×

Product 1

HCID 11361077N-(6-chloro-7-methylsulfanyl-9H-beta-carbolin-8-yl)-2-methyl-nicotinamideYield 89.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Conditions

Temperature
100 °C

Procedure

A 250 ml round-bottom flask with magnetic stirrer was charged with 6-chloro-7-methylsulfanyl-9H-β-carbolin-8-ylamine (Intermediate 28, 2.336 g, 8.86 mmol) and 2-methylnicotinic acid (3.219 g, 23.4 mmol) in 80 ml anhydrous pyridine. To the resulting reaction mixture at RT was added solid 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (7.080 g, 36.9 mmol) and the reaction mixture was heated to 100° C. (oil bath) for 2 days. The resulting mixture was cooled to RT and concentrated (rotavap) to afford a brown residue. The residue was redissolved in MeOH (50 ml), slowly added to a stirring mixture of 5:1H2O/saturated aqueous sodium bicarbonate (600 mlL) and stirred at RT for 18 hr. The precipitated solid was collected via suction filtration, washed with Et2O (2×150 ml), and air-dried to afford 3.036 g of crude N-(6-chloro-7-methylsulfanyl-9H-β-carbolin-8-yl)-2-methyl-nicotinamide as a brown solid. The crude material was purified via HPLC (yields=˜40-60%). 1H-NMR (300 MHz, DMSO-d6): δ 11.72 (1H, s) 10.50 (1H, s) 8.97 (1H, s) 8.62 (1H, dd) 8.57 (1H, s) 8.41 (1H, d) 8.33-8.27 (1H, m) 8.21 (1H, d) 2.73 (3H, s) 2.41 (3H, s). LCMS (ammonium acetate standard method) retention time=1.89 min. MS (M+H+): 383.

Workup

  1. customTo the resulting reaction mixture at RT
  2. temperatureThe resulting mixture was cooled to RT
  3. concentrationconcentrated (rotavap)
  4. customto afford a brown residue
  5. additionslowly added to a stirring mixture of 5
  6. filtrationThe precipitated solid was collected via suction filtration
  7. washwashed with Et2O (2×150 ml)
  8. customair-dried

Sources & evidence

ORD record
ord-44362255a3e24dc9b0ddfc92cb3cdcde
Source dataset
uspto-grants-2011_05
Patent number
US07951801B2

Reaction notes

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