Potassium Phosphate, Tribasic → 5-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine

HRID 634181Notes

Reaction equation

HRID 634181 reaction equation
[CH3:1][O:2][C:3]1[CH:43]=[CH:42][C:6]([CH2:7][NH:8][C:9]2[O:10][C:11]([C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[N:19]([S:23]([C:26]3[CH:32]=[CH:31][C:29]([CH3:30])=[CH:28][CH:27]=3)(=[O:25])=[O:24])[CH:18]=[C:17]4B3OC(C)(C)C(C)(C)O3)=[N:12][N:13]=2)=[CH:5][CH:4]=1.Br[C:45]1[CH:50]=[N:49][CH:48]=[C:47]([CH:51]2[CH2:53][CH2:52]2)[N:46]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>[CH:51]1([C:47]2[N:46]=[C:45]([C:17]3[C:16]4[C:20](=[CH:21][CH:22]=[C:14]([C:11]5[O:10][C:9]([NH:8][CH2:7][C:6]6[CH:42]=[CH:43][C:3]([O:2][CH3:1])=[CH:4][CH:5]=6)=[N:13][N:12]=5)[CH:15]=4)[N:19]([S:23]([C:26]4[CH:32]=[CH:31][C:29]([CH3:30])=[CH:28][CH:27]=4)(=[O:25])=[O:24])[CH:18]=3)[CH:50]=[N:49][CH:48]=2)[CH2:53][CH2:52]1

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 457883052-Bromo-6-cyclopropylpyrazineHCID 68328427N-(4-methoxybenzyl)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine

Product 1

HCID 683280565-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amineYield 68%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of N-(4-methoxybenzyl)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (240 mg, 0.400 mmol), 2-bromo-6-cyclopropylpyrazine (CombiPhos Catalysts, Inc., Princeton, N.J.; 88 mg, 0.440 mmol), potassium phosphate (255 mg, 1.199 mmol), Pd2(dba)3 (10.98 mg, 0.012 mmol), and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (XPhos; 11.43 mg, 0.024 mmol) in dioxane (4.0 mL) and water (0.400 mL) was sparged with argon then heated at 120° C. (microwave) for 20 min. The reaction was cooled to RT, diluted with DCM (20 mL), and concentrated onto silica gel. Chromatographic purification (silica gel, 0-100% EtOAc/Hex) furnished 5-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine (160 mg, 0.270 mmol, 68%) as a light-yellow solid: MS (ESI, pos. ion) m/z: 593.2 (M+1).

Workup

  1. customwas sparged with argon
  2. temperatureThe reaction was cooled to RT
  3. additiondiluted with DCM (20 mL)
  4. concentrationconcentrated onto silica gel
  5. customChromatographic purification (silica gel, 0-100% EtOAc/Hex)

Sources & evidence

ORD record
ord-7004fdd9dd974474ad551390d50efaba
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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