Ammonia → HCID 71263628, compound

HRID 2272332Notes

Reaction equation

HRID 2272332 reaction equation
C[N:2](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[B:25]([C:28]1[CH:33]=[CH:32][C:31]([N:34]([C:39]2[C:57]([CH:58]3[CH2:60][CH2:59]3)=[CH:56][C:42]3[C:43]([C:53]([OH:55])=O)=[C:44]([C:46]4[CH:51]=[CH:50][C:49]([Cl:52])=[CH:48][CH:47]=4)[O:45][C:41]=3[CH:40]=2)[S:35]([CH3:38])(=[O:37])=[O:36])=[CH:30][C:29]=1[Cl:61])([OH:27])[OH:26].CCN(C(C)C)C(C)C.N.CO>CN(C=O)C.CCOC(C)=O.O>[C:53]([C:43]1[C:42]2[CH:56]=[C:57]([CH:58]3[CH2:60][CH2:59]3)[C:39]([N:34]([C:31]3[CH:32]=[CH:33][C:28]([B:25]([OH:27])[OH:26])=[C:29]([Cl:61])[CH:30]=3)[S:35]([CH3:38])(=[O:36])=[O:37])=[CH:40][C:41]=2[O:45][C:44]=1[C:46]1[CH:47]=[CH:48][C:49]([Cl:52])=[CH:50][CH:51]=1)(=[O:55])[NH2:2]

Participants

9

Reactant 5

HCID 222AmmoniaHCID 887MethanolHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71263608HCID 71263608, compound

Product 1

HCID 71263628HCID 71263628, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (27.1 mg, 0.071 mmol) was added to a solution of 6-(N-(4-borono-3-chlorophenyl)methylsulfonamido)-2-(4-chlorophenyl)-5-cyclopropylbenzofuran-3-carboxylic acid (20 mg, 0.036 mmol) and Hunig's base (0.031 mL, 0.179 mmol) in DMF (3 mL). After stirring for 1 h at RT, a 2M solution of ammonia in MeOH (0.357 mL, 0.714 mmol) was added and the solution was stirred for 16 h. Water and EtOAc were added. The organic layer was separated, washed with water, brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by Reverse Phase HPLC (water/MeCN+0.1% formic acid) to give (4-(N-(3-carbamoyl-2-(4-chlorophenyl)-5-cyclopropylbenzofuran-6-yl)methylsulfonamido)-2-chlorophenyl)boronic acid (9 mg, 0.015 mmol, 43% yield) as a white powder. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.33 (s, 2H), 8.12 (s, 1H), 8.05 (s, 1H), 7.94-8.01 (m, 2H), 7.80 (s, 1H), 7.59-7.68 (m, 2H), 7.41-7.46 (m, 1H), 7.39 (d, 1H), 7.30-7.37 (m, 1H), 7.23 (s, 1H), 3.41 (s, 3H), 2.05-2.21 (m, 1H), 1.02 (br. s., 1H), 0.83 (br. s., 2H), 0.53 (br. s., 1H). LCMS (m/z, ES+)=559.2 (M+H+).

Workup

  1. stirringthe solution was stirred for 16 h
  2. customThe organic layer was separated
  3. washwashed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by Reverse Phase HPLC (water/MeCN+0.1% formic acid)

Sources & evidence

ORD record
ord-1f1ba43e01794233bbcd0f408f2feab5
Source dataset
uspto-grants-2015_09
Patent number
US09119868B2

Reaction notes

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