Cyclopropanecarbonyl chloride → N-(5-(3-(ethylsulfonyl)phenyl)-8-methoxy-3-methyl-9H-pyrido[2,3-b]indol-7-yl)-N-methylcyclopropanecarboxamide

HRID 1882285Notes

Reaction equation

HRID 1882285 reaction equation
[CH2:1]([S:3]([C:6]1[CH:7]=[C:8]([C:12]2[CH:20]=[C:19]([NH:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]3[C:13]=2[C:14]2[CH:28]=[C:27]([CH3:29])[CH:26]=[N:25][C:15]=2[NH:16]3)[CH:9]=[CH:10][CH:11]=1)(=[O:5])=[O:4])[CH3:2].[CH:30]1([C:33](Cl)=[O:34])[CH2:32][CH2:31]1>C1COCC1>[CH2:1]([S:3]([C:6]1[CH:7]=[C:8]([C:12]2[CH:20]=[C:19]([N:21]([CH3:22])[C:33]([CH:30]3[CH2:32][CH2:31]3)=[O:34])[C:18]([O:23][CH3:24])=[C:17]3[C:13]=2[C:14]2[CH:28]=[C:27]([CH3:29])[CH:26]=[N:25][C:15]=2[NH:16]3)[CH:9]=[CH:10][CH:11]=1)(=[O:5])=[O:4])[CH3:2]

Participants

4

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 588801275-(3-(ethylsulfonyl)phenyl)-8-methoxy-N,3-dimethyl-9H-pyrido[2,3-b]indol-7-amine

Product 1

HCID 58880140N-(5-(3-(ethylsulfonyl)phenyl)-8-methoxy-3-methyl-9H-pyrido[2,3-b]indol-7-yl)-N-methylcyclopropanecarboxamideYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Compound 252 (150 mg, 0.37 mmol) in dry THF (3 mL) was added cyclopropylcarbonyl chloride (34 μL, 0.37 mmol) at 0° C. Slowly the temperature was raised to room temperature and stirred for an additional hour. Reaction was quenched with aqueous NaHCO3 solution and extracted with EtOAc, washed with brine, dried over Na2SO4 and finally purified preparative HPLC to provide Compound 253 (132 mg, 75%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.63 (br. d, J=8.1 Hz, 2H) 0.80 (br. s., 2H) 1.18 (t, J=7.45 Hz, 3H) 1.48 (td, J=8.02, 3.92 Hz, 1H) 2.27 (s, 3H) 3.26 (s, 3H) 3.41 (q, J=7.45 Hz, 2H) 3.98 (s, 3H) 7.17 (s, 1H) 7.54 (s, 1H) 7.88 (t, J=7.71 Hz, 1H) 8.04 (d, J=8.08 Hz, 2H) 8.14 (s, 1H) 8.31 (d, J=1.26 Hz, 1H) 12.31 (s, 1H); [M+H] calc'd for C26H28N3O4S, 478.2; found, 478.3.

Workup

  1. customReaction
  2. customwas quenched with aqueous NaHCO3 solution
  3. extractionextracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4 and finally purified preparative HPLC

Sources & evidence

ORD record
ord-137b34cc24d241f294e6fab84cf8fba3
Source dataset
uspto-grants-2012_11
Patent number
US08318939B2

Reaction notes

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