Potassium Fluoride → HCID 66731042, compound

HRID 1028005Notes

Reaction equation

HRID 1028005 reaction equation
[C:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([CH:12]3CC3)=[CH:9][CH:10]=2)[N:5]([CH:15]2[CH2:18][CH2:17][CH2:16]2)[C:4]=1B(O)O)#[N:2].Cl[C:23]1[N:28]=[CH:27][C:26]([S:29]([NH:32][C@H:33]([CH3:38])[C:34]([F:37])([F:36])[F:35])(=[O:31])=[O:30])=[CH:25][CH:24]=1.F[B-](F)(F)F.[C:44]([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[F-:57].[K+]>C1COCC1.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]>[C:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([CH3:12])=[C:9]([F:57])[CH:10]=2)[N:5]([CH:15]2[CH2:18][CH2:17][CH2:16][CH2:44]2)[C:4]=1[C:23]1[N:28]=[CH:27][C:26]([S:29]([NH:32][C@H:33]([CH3:38])[C:34]([F:37])([F:36])[F:35])(=[O:31])=[O:30])=[CH:25][CH:24]=1)#[N:2]

Participants

7

Reactant 4

HCID 522689Potassium FluorideHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 667305423-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acidHCID 86668141(R)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide

Product 1

HCID 66731042HCID 66731042, compoundYield 94%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid prepared as above (6.0 g, 18.8 mmol, 90%), (R)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (3.63 g, 12.5 mmol) (similarly prepared as described in Example 4, Step A), tri-tert-butylphosphonium tetrafluoroborate (0.36 g, 1.2 mmol), Pd2(dba)3 (0.57 g, 0.62 mmol) and potassium fluoride (7.25 g, 125 mmol) in THF (80 mL) was stirred at 40° C. overnight. The solvent was then evaporated and the residue purified on silica gel eluting with a gradient of 0 to 10% ethyl acetate in CH2Cl2 to provide (R)-6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (5.83 g, 94%). Melting point: 191-193° C.; MS m/z 495.0 M+H+; 1H NMR (500 MHz, CDCl3): δ 9.24 (1H, t, J=1.1 Hz), 8.34 (1H, dd, J=8.3 Hz, J=2.4 Hz), 8.05 (1H, dd, J=8.3, 0.7 Hz), 7.43 (1H, d, J=9.2 Hz), 7.37 (1H, d, J=6.0 Hz), 5.26-5.19 (2H, m), 4.20-4.12 (1H, m), 2.46 (3H, d, J=1.9 Hz), 2.31-2.26 (2H, m), 2.20-2.16 (2H, m), 2.07-2.04 (2H, m), 1.80-1.76 (2H, m), 1.45 (3H, d, J=7.0 Hz).

Workup

  1. customsimilarly prepared
  2. customThe solvent was then evaporated
  3. customthe residue purified on silica gel eluting with a gradient of 0 to 10% ethyl acetate in CH2Cl2

Sources & evidence

ORD record
ord-fca459ee4ea24f97a86fa7db0b657ee3
Source dataset
uspto-grants-2014_05
Patent number
US08735414B2

Reaction notes

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