1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 5-(1-Methanesulfonyl-piperidin-4-ylamino)-pyridine-2-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide

HRID 1049021Notes

Reaction equation

HRID 1049021 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:19][CH:20]([CH3:22])[CH3:21])[S:9]([C:12]2[CH:17]=[CH:16][C:15](Br)=[CH:14][N:13]=2)(=[O:11])=[O:10])=[CH:4][CH:3]=1.[NH2:23][CH:24]1[CH2:29][CH2:28][N:27]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:26][CH2:25]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:19][CH:20]([CH3:22])[CH3:21])[S:9]([C:12]2[CH:17]=[CH:16][C:15]([NH:23][CH:24]3[CH2:29][CH2:28][N:27]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:26][CH2:25]3)=[CH:14][N:13]=2)(=[O:11])=[O:10])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 113558261-(Methanesulfonyl)piperidin-4-amineHCID 23676156Sodium t-butoxideHCID 867218735-Bromo-pyridine-2-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide

Product 1

HCID 867218745-(1-Methanesulfonyl-piperidin-4-ylamino)-pyridine-2-sulfonic acid (4-fluoro-phenyl)-isobutyl-amideYield 54.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 5-bromo-pyridine-2-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide (150 mg, 388 μmol), 4-amino-1-methanesulfonylpiperidine (82.8 mg, 465 μmol), Pd2(dba)3 (36 mg, 39 μmol), XantPhos (22 mg, 39 μmol), and sodium tert-butoxide (82 mg, 853 μmol) in toluene (4 mL) was degassed with nitrogen then heated at 125° C. for 30 minutes in a microwave reactor. Saturated aqueous NaHCO3 was added and then extracted with EtOAc, washed with brine, concentrated and purified by silica gel column chromatography (0-75% EtOAc in cyclohexane) to give the title compound (103 mg). 1H NMR (400 MHz, DMSO-d6): δ 8.10 (d, 1H), 7.36 (d, 1H), 7.15 (d, 4H), 6.96 (dd, 1H), 6.81 (d, 1H), 3.50-3.52 (m, 5H), 2.89 (s, 5H), 1.99 (s, 2H), 1.43-1.47 (m, 3H), 0.83 (d, 6H). LCMS (m/z, Method A) ES+ 484.9 [M+1]+.

Workup

  1. customwas degassed with nitrogen
  2. additionSaturated aqueous NaHCO3 was added
  3. extractionextracted with EtOAc
  4. washwashed with brine
  5. concentrationconcentrated
  6. custompurified by silica gel column chromatography (0-75% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-8429c453f7d94de188b46d63f50095da
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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