Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → HCID 59505157, compound

HRID 1672073Notes

Reaction equation

HRID 1672073 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[C:22]([CH3:32])=[CH:23][C:24]([O:30][CH3:31])=[C:25]([CH:29]=4)[C:26]([OH:28])=O)=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.Cl.[N:34]1[CH:39]=[CH:38][C:37]([C:40]2([NH2:43])[CH2:42][CH2:41]2)=[CH:36][N:35]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:29]=[C:25]([C:26](=[O:28])[NH:43][C:40]5([C:37]6[CH:38]=[CH:39][N:34]=[N:35][CH:36]=6)[CH2:42][CH2:41]5)[C:24]([O:30][CH3:31])=[CH:23][C:22]=4[CH3:32])=[CH:17][C:11]=3[C:12]=2[C:13]([NH:14][CH3:15])=[O:16])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 592756045-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoic acidHCID 67292500HCID 67292500, compound

Product 1

HCID 59505157HCID 59505157, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoic acid (0.080 g, 0.184 mmol, 1.0 eq), 1-(pyridazin-4-yl)cyclopropanamine HCl (0.025 g, 0.185 mmol, 1.0 eq) in DMF at 0° C. was added TEA (0.093 g, 0.920 mmol, 5.0 eq) and BOP reagent (0.120 g, 0.271 mmol, 1.5 eq). The reaction mixture was to stirred at RT overnight. The reaction mixture was diluted with water, extracted with EtOAc. The organic layer was washed with brine and dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel (60-120) column chromatography using 4% MeOH/CHCl3 as eluent and further purified by prep HPLC. Yield: 0.053 g (52.42%). 1H NMR (400 MHz, CD3OD): δ 9.21-9.16 (m, 2H), 8.01-7.94 (m, 2H), 7.81 (br. s., 1H), 7.77 (s, 1H), 7.66 (s, 1H), 7.60 (s, 1H), 7.34 (dd, J=1.8, 8.5 Hz, 1H), 7.32-7.25 (m, 2H), 7.17 (s, 1H), 4.10 (s, 3H), 2.96 (s, 3H), 2.38 (s, 3H), 1.75 (s, 4H). 19F NMR (376.51 MHz, CD3OD): δ−77.43 (TFA), −112.62. LCMS: (ES+) m/z=551.2 (M+H)+

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel (60-120) column chromatography
  7. customfurther purified by prep HPLC

Sources & evidence

ORD record
ord-ae10827de76f452fb7550bcab0576a83
Source dataset
uspto-grants-2011_08
Patent number
US07994171B2

Reaction notes

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