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

HRID 1987148Notes

Reaction equation

HRID 1987148 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:12](=[O:13])[C:11]3[C:14]([F:31])=[C:15]([NH:18][S:19]([N:22]([CH2:24][CH:25]4[CH2:30][O:29][CH2:28][CH2:27][O:26]4)[CH3:23])(=[O:21])=[O:20])[CH:16]=[CH:17][C:10]=3[CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.[CH3:32][N:33]1[CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:35]=[N:34]1.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[F-].[K+]>CN(C=O)C.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]>[O:26]1[CH2:27][CH2:28][O:29][CH2:30][CH:25]1[CH2:24][N:22]([CH3:23])[S:19]([NH:18][C:15]1[CH:16]=[CH:17][C:10]2[CH:9]=[CH:8][C:5]3=[N:6][CH:7]=[C:2]([C:36]4[CH:35]=[N:34][N:33]([CH3:32])[CH:37]=4)[CH:3]=[C:4]3[C:12](=[O:13])[C:11]=2[C:14]=1[F:31])(=[O:21])=[O:20]

Participants

7

Reactant 4

HCID 522689Potassium FluorideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 4060964Tri-t-butylphosphoniumHCID 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

Product 1

HCID 57722749N-(1,4-dioxan-2-ylmethyl)-N'-[6-fluoro-3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]-N-methylsulfamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 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 (127 mg, 0.271 mmol) in DMF (7 mL) were added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (113 mg, 0.543 mmol), tri-t-butylphosphonium tetraflroroborate (16 mg, 0.054 mmol), potassium fluoride (52 mg, 0.896 mmol), and Pd2(dba)3 (25 mg, 0.027 mmol). The reaction mixture was purged with N2 for 5 min, heated to 130 C for 9 h, cooled to room temperature, treated with water, and extracted with CH2Cl2 (×3). The combined organics were dried (Na2SO4), concentrated, and purified by prep-HPLC to afford the title compound. 1H NMR (600 MHz, CDCl3) δ 8.99 (d, 1H); 8.31 (d, 1H); 7.91 (s, 1H); 7.90 (m, 2H); 7.81 (s, 1H); 7.36 (d, 1H); 7.26 (d, 1H); 7.17 (d, 1H); 4.00 (s, 3H); 3.64-4.00 (series of m, 7H); 3.36 (dd, 1H); 3.09 (dd, 1H); 2.99 (s, 3H). LRMS (ESI) calc'd for (C24H24F5O5S) [M+H]+, 514.1; found 514.1.

Workup

  1. customThe reaction mixture was purged with N2 for 5 min
  2. temperatureheated to 130 C for 9 h
  3. additiontreated with water
  4. extractionextracted with CH2Cl2 (×3)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. concentrationconcentrated
  7. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-471150b22c434e99befa7978c7c1c0ff
Source dataset
uspto-grants-2009_06
Patent number
US07550478B2

Reaction notes

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