Diisopropylethylamine → (s)-5-(2-Hydroxy-benzoylamino)-1-methyl-1h-indole-2-carboxylic acid {2-[benzyl(methyl)amino]-2-oxo-1-phenylethyl}-amide

HRID 490011Notes

Reaction equation

HRID 490011 reaction equation
[OH:1][C:2]1[CH:23]=[CH:22][CH:21]=[CH:20][C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH3:16])[C:11]([C:17]([OH:19])=O)=[CH:10]2)=[O:5].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH2:48]([N:55]([CH3:66])[C:56](=[O:65])[C@H:57]([C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)[NH2:58])[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH2:48]([N:55]([CH3:66])[C:56](=[O:65])[C@@H:57]([NH:58][C:17]([C:11]1[N:12]([CH3:16])[C:13]2[C:9]([CH:10]=1)=[CH:8][C:7]([NH:6][C:4](=[O:5])[C:3]1[CH:20]=[CH:21][CH:22]=[CH:23][C:2]=1[OH:1])=[CH:15][CH:14]=2)=[O:19])[C:59]1[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=1)[C:49]1[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 222627095-(2-Hydroxy-benzoylamino)-1-methyl-1H-indole-2-carboxylic acidHCID 22691652(s)-n-Benzyl-n-methyl-2-phenylglycinamide

Product 1

HCID 23589010(s)-5-(2-Hydroxy-benzoylamino)-1-methyl-1h-indole-2-carboxylic acid {2-[benzyl(methyl)amino]-2-oxo-1-phenylethyl}-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

The product of step (b) (1.36 g, 4.38 mM), PyBrOP (2.45 g, 5.26 mM), and (S)-N-benzyl-N-methyl-2-phenylglycinamide (1.91 g, 6.57 mM) were placed in a 50 mL round bottom flask. DMF (20 mL) was added and the mixture was cooled to 0° C. and treated with diisopropyl ethylamine (3 mL, 17.52 mM). After the addition was complete the cooling bath was removed and the reaction mixture was stirred at room temperature for 16 h. The mixture was diluted with ethyl acetate (120 mL) and the mixture was washed with 1 N HCl (20 mL), water (20 mL) and brine (20 mL). The ethyl acetate was dried with MgSO4, filtered and concentrated. The residue was purified by flash column chromatography on silica gel eluting with 5% diethyl ether in CH2Cl2.

Workup

  1. additionAfter the addition
  2. customwas removed
  3. additionThe mixture was diluted with ethyl acetate (120 mL)
  4. washthe mixture was washed with 1 N HCl (20 mL), water (20 mL) and brine (20 mL)
  5. dry with materialThe ethyl acetate was dried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography on silica gel eluting with 5% diethyl ether in CH2Cl2

Sources & evidence

ORD record
ord-e1631f91393346099445e40911b14a0e
Source dataset
uspto-grants-2005_12
Patent number
US06979692B2

Reaction notes

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