Potassium Phosphate, Tribasic → N'-(3-chloro-6-fluoro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-(1,4-dioxan-2-ylmethyl)-N-methylsulfamide

HRID 1987147Notes

Reaction equation

HRID 1987147 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[CH:9][C:10]2[CH:21]=[CH:20][C:14]3=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=[C:13]3[C:12](=[O:22])[C:11]=2[C:23]=1[F:24])(=O)=O.[O:27]1[CH2:32][CH2:31][O:30][CH2:29][CH:28]1[CH2:33][N:34]([CH3:39])[S:35]([NH2:38])(=[O:37])=[O:36].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.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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]>[Cl:19][C:17]1[CH:18]=[C:13]2[C:12](=[O:22])[C:11]3[C:23]([F:24])=[C:7]([NH:38][S:35]([N:34]([CH2:33][CH:28]4[CH2:29][O:30][CH2:31][CH2:32][O:27]4)[CH3:39])(=[O:36])=[O:37])[CH:8]=[CH:9][C:10]=3[CH:21]=[CH:20][C:14]2=[N:15][CH:16]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 577229423-chloro-6-fluoro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl trifluoromethanesulfonateHCID 58775672N-(1,4-dioxan-2-ylmethyl)-N-methylsulfamide

Product 1

HCID 57722790N'-(3-chloro-6-fluoro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-(1,4-dioxan-2-ylmethyl)-N-methylsulfamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of 3-chloro-6-fluoro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl trifluoromethanesulfonate (200 mg, 0.49 mmol) in 1,4-dioxane (7 mL) were added N-(1,4-dioxan-2-ylmethyl)-N-methylsulfamide (200 mg, 0.98 mmol), Pd2(dba)3 (68 mg, 0.074 mmol), Xantphos (85 mg, 0.15 mmol), and K3PO4 (280 mg, 1.3 mmol). The reaction mixture was purged with N2 for 5 min, heated to 110° C. 8 h, cooled to room temperature, diluted with water, and extracted with CH2Cl2 (×3). The combined organics were dried (Na2SO4), concentrated, and purified by flash chromatography to afford the title compound. 1H NMR (600 MHz, CDCl3) δ 8.78 (d, 1H); 8.24 (d, 1H); 7.99 (d, 1H); 7.93 (t, 1H); 7.36 (d, 1H); 7.21 (br s, 2H); 3.64-4.00 (series of m, 7H); 3.36 (dd, 1H); 3.08 (dd, 1H); 2.99 (s, 3H). LRMS (ESI) calc'd for (C20H19ClFN3O5S) [M+H]+, 468.1; found 468.0.

Workup

  1. customThe reaction mixture was purged with N2 for 5 min
  2. temperature8 h, cooled to room temperature
  3. additiondiluted with water
  4. extractionextracted with CH2Cl2 (×3)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. concentrationconcentrated
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-4c2cf18cf44d4e91b9dbb79852539cfa
Source dataset
uspto-grants-2009_06
Patent number
US07550478B2

Reaction notes

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