Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → HCID 59505149, compound

HRID 1672077Notes

Reaction equation

HRID 1672077 reaction equation
[F:1][C:2]1[C:7]2[C:8]([C:18](=[O:21])[NH:19][CH3:20])=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=1[CH3:31])[C:25]([OH:27])=O.Cl.[N:33]1[CH:38]=[CH:37][C:36]([C:39]2([NH2:42])[CH2:41][CH2:40]2)=[CH:35][N:34]=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[C:7]2[C:8]([C:18]([NH:19][CH3:20])=[O:21])=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[CH:23]=[C:24]([C:25](=[O:27])[NH:42][C:39]2([C:36]3[CH:37]=[CH:38][N:33]=[N:34][CH:35]=3)[CH2:41][CH2:40]2)[CH:28]=[CH:29][C:30]=1[CH3:31]

Participants

6

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 592756803-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acidHCID 67292500HCID 67292500, compound

Product 1

HCID 59505149HCID 59505149, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid (0.050 g, 0.114 mmol, 1.0 eq), 1-(pyridazin-4-yl)cyclopropanamine HCl (0.015 g, 0.113 mmol, 1.0 eq) in DMF at 0° C. was added TEA (0.060 g, 0.594 mmol, 5.0 eq) and BOP reagent (0.076 g, 0.172 mmol, 1.5 eq). The reaction mixture was stirred at RT. overnight. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by preparative HPLC. Yield: 0.030 g (50.0%). 1H NMR (400 MHz, CDCl3): δ 9.03 (d, J=5.6 Hz, 1H), 8.98 (m, 1H), 8.01-7.98 (m., 2H), 7.81-7.78 (dd, J=2.0, 8.0 Hz, 1H), 7.73 (d, J=2 Hz, 1H), 7.44 (d, J=8.4, 2H), 7.28-7.26 (dd, 1H), 7.23-7.18 (m, 3H), 7.08 (s, 1H), 6.20 (bs, 1H), 3.04 (d, J=5.2 Hz, 3H), 2.29 (s, 3H), 1.61-1.54 (m, 4H). 19F NMR (376.57 MHz, CDCl3): δ−109.53, −119.52. LCMS: (ES+) m/z=539.2 (M+H)+

Workup

  1. customovernight
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-6421406df27f43ba9c03cdfecc126851
Source dataset
uspto-grants-2011_08
Patent number
US07994171B2

Reaction notes

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