Hydrochloric Acid → HCID 66730793, compound

HRID 1028026Notes

Reaction equation

HRID 1028026 reaction equation
BrC1C=C2C([C:6]([C:31]#N)=C(C3N=CC(S(NC(C)(C)C)(=O)=O)=CC=3)N2C2N=CC=CN=2)=CC=1F.Br[C:35]1[CH:43]=[C:42]2[C:38]([C:39](Cl)=[C:40]([C:50]3[N:55]=[CH:54][C:53]([S:56]([NH:59][C:60]([CH3:63])([CH3:62])[CH3:61])(=[O:58])=[O:57])=[CH:52][CH:51]=3)[N:41]2[C:44]2[N:49]=[CH:48][CH:47]=[CH:46][N:45]=2)=[CH:37][C:36]=1[F:65].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=[O:96].[K+].[K+].[CH:101]([O:103]CCCC)=[CH2:102].Cl>CN(C=O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:60]([NH:59][S:56]([C:53]1[CH:54]=[N:55][C:50]([C:40]2[N:41]([C:44]3[N:45]=[CH:46][CH:47]=[CH:48][N:49]=3)[C:42]3[C:38]([C:39]=2[C:101](=[O:103])[CH3:102])=[CH:37][C:36]([F:65])=[C:35]([C:31](=[O:96])[CH3:6])[CH:43]=3)=[CH:51][CH:52]=1)(=[O:58])=[O:57])([CH3:62])([CH3:61])[CH3:63]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl etherHCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 66730646HCID 66730646, compoundHCID 66730829HCID 66730829, compound

Product 1

HCID 66730793HCID 66730793, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 6-(6-bromo-3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N-tert-butylpyridine-3-sulfonamide and 6-(6-bromo-3-chloro-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N-tert-butylpyridine-3-sulfonamide (84 mg, 0.156 mmol), Pd(OAc)2 (7.6 mg, 0.034 mmol), 1,3-bis(diphenylphosphino)propane (31 mg, 0.075 mmol), K2CO3 (0.19 g, 1.36 mmol), butyl vinyl ether (0.73 mL, 5.66 mmol) in DMF (3.0 mL) and water (0.35 mL) was stirred at 120° C. overnight under N2 atmosphere. The mixture was then acidified to pH ˜1 with 1 N HCl, stirred at room temperature for 1 hr, extracted with ethyl acetate followed by drying with Na2SO4, evaporation and purification by flash chromatography with 5 to 20% ethyl acetate in CH2Cl2 to give N-tert-butyl-6-(3,6-diacetyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)pyridine-3-sulfonamide (58 mg, 73%). MS m/z 510.1 M+H+; 1H NMR (500 MHz, acetone-d6): δ 9.07 (1H, d, J=2.2 Hz), 8.77 (1H, d, J=6.2 Hz), 8.58 (2H, d, 4.9 Hz), 8.28 (1H, dd, J=8.2, 2.2 Hz), 8.12 (1H, d, J=10.2 Hz), 7.78 (1H, dd, J=8.2, 0.7 Hz), 7.21 (1H, t, J=4.9 Hz), 4.80 (1H, br s), 2.75 (3H, d, J=5.4 Hz), 2.21 (3H, s), 1.25 (9H, s).

Workup

  1. stirringstirred at room temperature for 1 hr
  2. extractionextracted with ethyl acetate
  3. dry with materialby drying with Na2SO4, evaporation and purification by flash chromatography with 5 to 20% ethyl acetate in CH2Cl2

Sources & evidence

ORD record
ord-b3a8ae1d109849e088d051fae0e0eafb
Source dataset
uspto-grants-2014_05
Patent number
US08735414B2

Reaction notes

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