Potassium Carbonate → HCID 57732876, compound

HRID 1806373Notes

Reaction equation

HRID 1806373 reaction equation
[CH:1]1([CH2:7][NH:8][CH2:9][C:10]2[S:14][C:13](B(O)O)=[CH:12][CH:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.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>[CH:1]1([CH2:7][NH:8][CH2:9][C:10]2[S:14][C:13]([C:19]3[CH:20]=[C:21]4[C:25](=[C:26]([C:28]([NH2:30])=[O:29])[CH:27]=3)[NH:24][CH:23]=[C:22]4[CH:31]3[CH2:32][CH2:33][N:34]([S:37]([CH2:40][CH3:41])(=[O:38])=[O:39])[CH2:35][CH2:36]3)=[CH:12][CH:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 113844275-bromo-3-[1-(ethanesulfonyl)-4-piperidinyl]-1H-indole-7-carboxamideHCID 66723132HCID 66723132, compound

Product 1

HCID 57732876HCID 57732876, compoundYield 6%

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), (cyclohexylmethyl)amine (37 mg, 0.32 mmol), and NaCNBH3 (40 mg, 0.64 mmol) were reacted to give 30 mg of crude (5-{[(cyclohexylmethyl)amino]methyl}-2-thienyl)boronic acid. The crude (5-{[(cyclohexylmethyl)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 once 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 4.7 mg of the title compound (6%).

Workup

  1. customThe crude product was purified once 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

Sources & evidence

ORD record
ord-4054a61d24ea444d8c0bae68c4b150de
Source dataset
uspto-grants-2013_01
Patent number
US08354406B2

Reaction notes

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