Cesium carbonate → HCID 66722841, compound

HRID 1806305Notes

Reaction equation

HRID 1806305 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:19][CH2:18][N:17]([S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[CH2:16][CH2:15]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:31][C:32]([O:35][C:36]([N:38]1[CH2:43][CH2:42][N:41]([C:44]2[N:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=2)[CH2:40][CH2:39]1)=[O:37])([CH3:34])[CH3:33]>O1CCOCC1.O.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>[NH2:13][C:11]([C:9]1[CH:10]=[C:2]([C:47]2[CH:46]=[CH:45][C:44]([N:41]3[CH2:42][CH2:43][N:38]([C:36]([O:35][C:32]([CH3:34])([CH3:33])[CH3:31])=[O:37])[CH2:39][CH2:40]3)=[N:49][CH:48]=2)[CH:3]=[C:4]2[C:8]=1[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:19][CH2:18][N:17]([S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[CH2:16][CH2:15]1)=[O:12]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 113844275-bromo-3-[1-(ethanesulfonyl)-4-piperidinyl]-1H-indole-7-carboxamideHCID 53216586{6-[4-(tert-Butoxycarbonyl)piperazin-1-yl]pyridin-3-yl}boronic acid

Product 1

HCID 66722841HCID 66722841, compoundYield 89.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (100 mg, 0.241 mmol) in dioxane (1.0 mL) and H2O (0.8 mL) was added cesium carbonate (314 mg, 0.964 mmol), and [6-(4-{[(1,1-dimethylethyl)oxy]carbonyl}-1-piperazinyl)-3-pyridinyl]boronic acid (297 mg, 0.964 mmol). The reaction mixture was stirred before addition of tetrakis(triphenylphosphine)palladium(0) (28 mg, 0.024 mmol). The reaction was heated in a microwave at 160° C. for 20 min. Mixture was concentrated and taken up in EtOAc (10 mL) and H2O (5.0 mL). Compound was purified by Gilson Preparatory HPLC to give 129 mg of 1,1-dimethylethyl 4-(5-{7-(aminocarbonyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indol-5-yl}-2-pyridinyl)-1-piperazinecarboxylate and 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-[6-(1-piperazinyl)-3-pyridinyl]-1H-indole-7-carboxamide (44%).

Workup

  1. concentrationMixture was concentrated
  2. customCompound was purified by Gilson Preparatory HPLC

Sources & evidence

ORD record
ord-3faac65e8a1646aeacb5b4e5f000bf4b
Source dataset
uspto-grants-2013_01
Patent number
US08354406B2

Reaction notes

Loading…