Potassium Phosphate, Tribasic → 3-(2-Chloro-4-methylsulfanyl-phenylamino)-1-methyl-1H-indole-2-carboxylic acid ethyl ester

HRID 2264940Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:16])[C:8]2[C:13]([C:14]=1[NH2:15])=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])[CH3:2].Br[C:18]1[CH:23]=[CH:22][C:21]([S:24][CH3:25])=[CH:20][C:19]=1[Cl:26].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:16])[C:8]2[C:13]([C:14]=1[NH:15][C:18]1[CH:23]=[CH:22][C:21]([S:24][CH3:25])=[CH:20][C:19]=1[Cl:26])=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

3-Amino-1-methyl-1H-indole-2-carboxylic acid ethyl ester (200 mg, 0.91 mmol) and 1-bromo-2-chloro-4-methylsulfanyl-benzene (304 mg, 1.28 mmol) were dissolved in toluene (5 ml) and Pd2(dba)3 (42 mg, 0.05 mmol) was added, followed by Xantphos (53 mg, 0.09 mmol) and potassium phosphate tribasic (386 mg, 1.82 mmol). The mixture was degassed and purged with argon, then stirred under argon at 120° C. for 16 hours. After cooling, the mixture was filtered through celite then concentrated. Purification of the resultant residue by flash chromatography (Si-PCC, ether:pentane gradient 1:4 to 1:0) gave the title compound as a yellow oil (300 mg, 88%). LCMS (method B): RT=2.64, M+H+ 376/378.

Workup

customThe mixture was degassed
custompurged with argon
temperatureAfter cooling
filtrationthe mixture was filtered through celite
concentrationthen concentrated
customPurification of the resultant residue by flash chromatography (Si-PCC, ether:pentane gradient 1:4 to 1:0)

Sources & evidence

ORD record: ord-a6d1f3377ad84958a0e57216611ecea9
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07855216B2

Reaction notes

Loading…