Diisopropylethylamine → HCID 11619860, compound

HRID 230748Notes

Reaction equation

HRID 230748 reaction equation
[ClH:1].[NH2:2][C:3]1[C:8]2[CH:9]=[CH:10][N:11]([C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19](NC(=O)CC4C=CC(F)=CC=4)=[O:20])=[CH:14][CH:13]=3)[C:7]=2[CH:6]=[CH:5][N:4]=1.[F:32][C:33]1[CH:38]=[CH:37][C:36]([N:39]2[CH:44]=[CH:43][CH:42]=[C:41](C(O)=O)[C:40]2=[O:48])=[CH:35][CH:34]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[ClH:1].[NH2:2][C:3]1[C:8]2[CH:9]=[CH:10][N:11]([C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19]([C:41]4[C:40](=[O:48])[N:39]([C:36]5[CH:37]=[CH:38][C:33]([F:32])=[CH:34][CH:35]=5)[CH:44]=[CH:43][CH:42]=4)=[O:20])=[CH:14][CH:13]=3)[C:7]=2[CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11590275HCID 11590275, compound2×HCID 210815271-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid

Product 1

HCID 11619860HCID 11619860, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Bis-tert-butyl 1-(4-aminophenyl)-1H-pyrrolo[3,2-c]pyridin-4-yl-dicarbamate (Compound B of Example 3, 0.18 g, 0.043 mmol, 1.0 eq) was added to a solution of 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (0.011 g, 0.047 mmol, 1.1 eq) and TBTU (0.018, 0.047 mmol, 1.1 eq) in DMF (0.50 mL) at room temperature. Diisopropylethylamine (0.008 mL, 0.047 mmol, 1.1 eq) was added to the reaction mixture and stirring was continued for 8 h. The reaction mixture was concentrated in vacuo and the residue was purified by reverse phase HPLC (YMC C-18 column, 30 min. gradient 25-90% aq. MeOH with 0.1% TFA). The appropriate fractions were concentrated in vacuo and the residue treated with anhydrous HCl (4 N in dioxane) at 0° C. The solution was concentrated in vacuo and the later procedure repeated three times. The residue was triturated with Et2O, discarding the filtrate and the solid was dried in vacuo to afford the title compound (0.003 g, 17%) as a white solid. 1H NMR (CD3OD) δ 7.85-7.87 (m, 2H), 7.56-7.63 (m, 3H), 7.24-7.46 (m, 6H), 7.03-7.09 (m, 3H), 6.94 (br m, 1H); MS(ESI+) m/z 440 (M+H)+, calc: 440.1523, found: 440.1517.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was purified by reverse phase HPLC (YMC C-18 column, 30 min. gradient 25-90% aq. MeOH with 0.1% TFA)
  3. concentrationThe appropriate fractions were concentrated in vacuo
  4. additionthe residue treated with anhydrous HCl (4 N in dioxane) at 0° C
  5. concentrationThe solution was concentrated in vacuo
  6. customThe residue was triturated with Et2O
  7. customthe solid was dried in vacuo

Sources & evidence

ORD record
ord-de69724a708b4bc0aa20766aa91fe282
Source dataset
uspto-grants-2009_07
Patent number
US07566784B2

Reaction notes

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