Potassium Carbonate → 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-[5-({[3-(propyloxy)propyl]amino}methyl)-2-thienyl]-1H-indole-7-carboxamide

HRID 562193Notes

Reaction equation

HRID 562193 reaction equation
[CH2:1]([O:4][CH2:5][CH2:6][CH2:7][NH:8][CH2:9][C:10]1[S:14][C:13](B(O)O)=[CH:12][CH:11]=1)[CH2:2][CH3:3].Br[C:19]1[CH:20]=[C:21]2[C:25](=[C:26]([C:28]([NH2:30])=[O:29])[CH:27]=1)[NH:24][CH:23]=[C:22]2[CH:31]1[CH2:36][CH2:35][N:34]([S:37]([CH2:40][CH3:41])(=[O:39])=[O:38])[CH2:33][CH2:32]1.C([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:40]([S:37]([N:34]1[CH2:33][CH2:32][CH:31]([C:22]2[C:21]3[C:25](=[C:26]([C:28]([NH2:30])=[O:29])[CH:27]=[C:19]([C:13]4[S:14][C:10]([CH2:9][NH:8][CH2:7][CH2:6][CH2:5][O:4][CH2:1][CH2:2][CH3:3])=[CH:11][CH:12]=4)[CH:20]=3)[NH:24][CH:23]=2)[CH2:36][CH2:35]1)(=[O:39])=[O:38])[CH3:41]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 113844275-bromo-3-[1-(ethanesulfonyl)-4-piperidinyl]-1H-indole-7-carboxamideHCID 66723096[5-({[3-(Propyloxy)propyl]amino}methyl)-2-thienyl]boronic acid

Product 1

HCID 577326283-[1-(ethylsulfonyl)-4-piperidinyl]-5-[5-({[3-(propyloxy)propyl]amino}methyl)-2-thienyl]-1H-indole-7-carboxamideYield 2%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

Following the general procedure of 5-(5-{[(2-ethylbutyl)amino]methyl}-2-thienyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide, (5-formyl-2-thienyl)boronic acid (50 mg, 0.32 mmol), [3-(propyloxy)propyl]amine (38 mg, 0.32 mmol), and NaCNBH3 (40 mg, 0.64 mmol) were reacted to give 30 mg of crude [5-({[3-(propyloxy)propyl]amino}methyl)-2-thienyl]boronic acid. The crude [5-({[3-(propyloxy)propyl]amino}methyl)-2-thienyl]boronic acid was then reacted with 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (65 mg, 0.157 mmol), K2CO3 (130 mg, 0.942 mmol), and tetrakis(triphenylphosphine)palladium(0) (9 mg, 0.0079 mmol). The crude product was purified twice on an Agilent MDAP using the procedure shown in preparation of 5-(5-{[(2-ethylbutyl)amino]methyl}-2-thienyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide. The purified product was washed with a 20:4:1 mixture of hexanes/EtOAc/MeOH (2.5 mL), taken up in EtOAc (2 mL) and washed with saturated K2CO3 (1 mL). The organic layer was concentrated to give to give 1.4 mg of the title compound (2%).

Workup

  1. customThe crude product was purified twice on an Agilent MDAP
  2. customshown in preparation of 5-(5-{[(2-ethylbutyl)amino]methyl}-2-thienyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide
  3. washThe purified product was washed with a 20:4:1 mixture of hexanes/EtOAc/MeOH (2.5 mL)
  4. washwashed with saturated K2CO3 (1 mL)
  5. concentrationThe organic layer was concentrated
  6. customto give

Sources & evidence

ORD record
ord-bb5006f99fff44979e1b8bd7e77cae52
Source dataset
uspto-grants-2011_11
Patent number
US08063071B2

Reaction notes

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