Ammonia → HCID 71263628, compound

HRID 1424834Notes

Reaction equation

HRID 1424834 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-3128d6037ad147b7b420c36d57ac2564
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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