1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → [3-((4-(4-Fluoro-2-methoxyphenyl)pyridin-2-yl)amino)phenyl]-methanesulfonamide

HRID 593286Notes

Reaction equation

HRID 593286 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=2[O:15][CH3:16])[CH:5]=[CH:4][N:3]=1.[NH2:17][C:18]1[CH:19]=[C:20]([CH2:24][S:25]([NH2:28])(=[O:27])=[O:26])[CH:21]=[CH:22][CH:23]=1.O(C(C)(C)C)[Na].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:17][C:18]3[CH:19]=[C:20]([CH2:24][S:25]([NH2:28])(=[O:26])=[O:27])[CH:21]=[CH:22][CH:23]=3)[CH:7]=2)=[C:9]([O:15][CH3:16])[CH:10]=1

Participants

6

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 13266255(3-Aminophenyl)methanesulfonamideHCID 584326092-Chloro-4-(4-fluoro-2-methoxyphenyl)pyridineHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 60172239[3-((4-(4-Fluoro-2-methoxyphenyl)pyridin-2-yl)amino)phenyl]-methanesulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

Intermediate A2 (119 mg, 0.5 mmol), (3-aminophenyl)methanesulfonamide (112 mg, 0.6 mmol), NaOC(CH3)3 (67 mg, 0.7 mmol), PdCl2(CH3CN)2 (6.5 mg, 0.025 mmol, 5 mol %), and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) [Xantphos] (23 mg, 0.04 mmol, 8 mol %) were dissolved in dry DMF (4 mL) and purged for 10 minutes with nitrogen. After heating at 110° C. for 18 hours the reaction mixture was filtered and the residue washed with toluene. The filtrate was concentrated under reduced pressure and purified by automated column chromatography (ISCO, gradient MeOH/DCM). The collected fractions which contained the title compound were further purified by preparative HPLC to yield 24 mg (12%) of G1 as an off-white solid. 1H NMR (300 MHz, d6-DMSO, 298K) δ 3.84 (s, 3H), 4.22 (s, 2H), 6.81-6.94 (m, 5H), 6.98 (s, 1H), 7.07 (dd, J=11.7 Hz, J=4.2 Hz, 1H), 7.26 (t, J=6.6 Hz, 1H), 7.39 (dd, J=6.9 Hz, J=6.0 Hz, 1H), 7.56-7.61 (m, 1H), 7.79 (d, J=7.5 Hz, 1H), 8.16 (d, J=6.0 Hz, 1H), 9.12 (s, 1H).

Workup

  1. custompurged for 10 minutes with nitrogen
  2. filtrationwas filtered
  3. washthe residue washed with toluene
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. custompurified by automated column chromatography (ISCO, gradient MeOH/DCM)
  6. customwere further purified by preparative HPLC
  7. customto yield 24 mg (12%) of G1 as an off-white solid

Sources & evidence

ORD record
ord-c67929852bdb4a339566a7461158a5dd
Source dataset
uspto-grants-2016_01
Patent number
US09242937B2

Reaction notes

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