Trifluoroacetic acid → HCID 58328161, compound

HRID 1951277Notes

Reaction equation

HRID 1951277 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[CH3:14])[C:5]([NH:7][CH:8]1[CH2:10][CH2:9]1)=[O:6].[CH2:15]([O:17][C:18]([N:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([C:29](O)=[O:30])[CH:27]=2)[CH:22]=[CH:21]1)=[O:19])[CH3:16].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(O)(C(F)(F)F)=O>CN(C=O)C.CO.O>[CH:8]1([NH:7][C:5]([C:4]2[CH:11]=[CH:12][C:13]([CH3:14])=[C:2]([NH:1][C:29]([C:26]3[CH:27]=[C:28]4[C:23]([CH:22]=[CH:21][N:20]4[C:18]([O:17][CH2:15][CH3:16])=[O:19])=[CH:24][CH:25]=3)=[O:30])[CH:3]=2)=[O:6])[CH2:9][CH2:10]1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acid2×HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 119838543-amino-N-cyclopropyl-4-methylbenzamideHCID 67148960HCID 67148960, compound

Product 1

HCID 58328161HCID 58328161, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent3×HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-amino-N-cyclopropyl-4-methylbenzamide (0.025 g, 0.11 mmol) in anhydrous DMF (0.5 mL), are sequentially added 1-(ethoxycarbonyl)-1H-indole-6-carboxylic acid (0.026 g, 0.11 mmol, prepared according to a similar procedure outlined for step A, Example 128 in WO 2002/014308) triethylamine (61 μL, 0.44 mmol) and BOP (0.098 g, 0.22 mmol) at room temperature. The reaction mixture was stirred at room temperature for 18 h, diluted with MeOH (0.5 mL) and subjected to reverse phase preparative HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA). The desired fractions were collected, and concentrated using speedVac® Plus (SC250DDA) to yield the title compound (Example 218, 0.010 g). HPLC Ret. time (YMC S5 Combiscreen ODS; 4.6×50 mm (4 min. gradient); Solvent A=10% MeOH, 90% H2O, 0.2% H3PO4; solvent B=90% MeOH, 10% H2O, 0.2% H3PO4): 3.18 min. LCMS [M+H]+ 406.3.

Workup

  1. customprepared
  2. customat room temperature
  3. customThe desired fractions were collected
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-cfe42622e1434649966352fbca8618d7
Source dataset
uspto-grants-2013_03
Patent number
US08404689B2

Reaction notes

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