Diisopropylethylamine → N-(2-Amino-2-oxoethyl)-1-(5-bromopyrimidin-2-yl)-N-methyl-3-(methylsulfinyl)-1H-indole-6-carboxamide

HRID 630520Notes

Reaction equation

HRID 630520 reaction equation
C([N:4](C(C)C)CC)(C)C.[Br:10][C:11]1[CH:12]=[N:13][C:14]([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]([N:28]([CH2:30][C:31](O)=[O:32])[CH3:29])=[O:27])[CH:24]=3)[C:19]([S:34]([CH3:36])=[O:35])=[CH:18]2)=[N:15][CH:16]=1.BrC1C=NC(N2C3C(=CC=C(C(O)=O)C=3)C(SC)=C2)=NC=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.CNCC(OC)=O>CN(C=O)C>[NH2:4][C:31](=[O:32])[CH2:30][N:28]([CH3:29])[C:26]([C:23]1[CH:24]=[C:25]2[C:20]([C:19]([S:34]([CH3:36])=[O:35])=[CH:18][N:17]2[C:14]2[N:13]=[CH:12][C:11]([Br:10])=[CH:16][N:15]=2)=[CH:21][CH:22]=1)=[O:27]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 83544Glycine, N-methyl-, methyl ester, hydrochloride (1:1)HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 1186660601-(5-Bromopyrimidin-2-yl)-3-(methylthio)-1H-indole-6-carboxylic acidHCID 1186768662-(1-(5-bromopyrimidin-2-yl)-N-methyl-3-(methylsulfinyl)-1H-indole-6-carboxamido)acetic acid

Product 1

HCID 118666048N-(2-Amino-2-oxoethyl)-1-(5-bromopyrimidin-2-yl)-N-methyl-3-(methylsulfinyl)-1H-indole-6-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Diisopropylethylamine (0.34 mL, 1.99 mmol), EDCxHCl (0.19 g, 0.992 mmol) and HOBt ammonium salt (0.15 g, 0.997 mmol) were added to 2-(1-(5-bromopyrimidin-2-yl)-N-methyl-3-(methylsulfinyl)-1H-indole-6-carboxamido)acetic acid (0.3 g, 0.66 mmol, synthesized from 1-(5-bromopyrimidin-2-yl)-3-(methylthio)-1H-indole-6-carboxylic acid in three steps comprising a TBTU mediated amide coupling of methyl 2-(methylamino)acetate hydrochloride, the oxidation of the thioether and the hydrolysis of the methyl ester) in DMF (3.0 mL). The reaction mixture was stirred at room temperature for 16 h, diluted with ice water and extracted with methanol/dichloromethane (5:95; 3×40 mL). The combined organic layers were successively washed with saturated sodium hydrogen carbonate, saturated ammonium chloride solution, and brine, dried over sodium sulfate and concentrated to yield the raw product which was purified by column chromatography [silica; methanol/dichloromethane=5:95]. White solid. Yield: 0.13 g (43% of theory)

Workup

  1. extractionextracted with methanol/dichloromethane (5:95; 3×40 mL)
  2. washThe combined organic layers were successively washed with saturated sodium hydrogen carbonate, saturated ammonium chloride solution, and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-f612817665314a97bdfd2ea09500d7d7
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

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