Morpholine → HCID 86694525, compound

HRID 1406559Notes

Reaction equation

HRID 1406559 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[N:16]([C:17]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:18]=3[CH:19]=[CH:20][CH:21]=[N:22]4)[N:15]=[C:14]([CH3:27])[CH:13]=2)(=[O:10])=[O:9])=[CH:4][C:3]=1[F:28].[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.OP([O-])(O)=O.[K+]>CN(C)C=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:28][C:3]1[CH:4]=[C:5]([S:8]([NH:11][C:12]2[N:16]([C:17]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:18]=3[CH:19]=[CH:20][CH:21]=[N:22]4)[N:15]=[C:14]([CH3:27])[CH:13]=2)(=[O:10])=[O:9])[CH:6]=[CH:7][C:2]=1[N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 516951Monobasic potassium phosphateHCID 634876Binap, (A+-)-HCID 86694526HCID 86694526, compound

Product 1

HCID 86694525HCID 86694525, compoundYield 73.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A stirring mixture of 4-bromo-3-fluoro-N-(3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-yl)benzenesulfonamide (0.07 g, 0.15 mmol), morpholine (0.066 g, 0.75 mmol), tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3, 0.007 g, 0.008 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP, 0.014 g, 0.023 mmol), and potassium phosphate monobasic (K3PO4.H2O, 0.21 g, 0.90 mmol) in anhydrous N,N-dimethylformamide (DMF, 6 mL) was purged with nitrogen for 5 min. The reaction mixture was heated at 90° C. for 4 h. After cooling to room temperature, ethyl acetate (10 mL) was added to the reaction mixture and washed with aqueous saturated sodium bicarbonate. The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The resulting crude material was purified by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the title compound as a white solid (0.049 g, 0.11 mmol, 70%). 1H NMR (400 MHz, CDCl3) δ 9.06 (dd, J=1.6, 4.8 Hz, 1H), 8.36 (d, J=8.4 Hz, 1H), 8.31 (d, J=8.0 Hz, 1H), 7.88 (dd, J=8.4, 9.6 Hz, 1H), 7.68 (d, J=4.8 Hz, 1H), 7.66 (d, J=6.4 Hz, 1H), 7.37 (dd, J=1.6, 8.4 Hz, 1H), 7.31 (dd, J=2.4, 12.4 Hz, 1H), 6.80 (t, J=6.8 Hz, 1H), 6.09 (s, 1H), 3.90-3.86 (m, 4H), 3.21-3.18 (m, 4H), 2.35 (s, 3H); MS: (ES) m/z calculated for C23H23FN5O3S [M+H+ 468.2. found 468.2.

Workup

  1. customwas purged with nitrogen for 5 min
  2. temperatureAfter cooling to room temperature
  3. additionethyl acetate (10 mL) was added to the reaction mixture
  4. washwashed with aqueous saturated sodium bicarbonate
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting crude material was purified by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-7732a66c070c47e087b198306e955926
Source dataset
uspto-grants-2014_12
Patent number
US08916601B2

Reaction notes

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