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

HRID 634226Notes

Reaction equation

HRID 634226 reaction equation
CC1(C)C(C)(C)OB([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]4[O:22][C:21]([NH:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[N:20][N:19]=4)[CH:16]=3)[N:11]([S:29]([C:32]3[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=3)(=[O:31])=[O:30])[CH:10]=2)O1.Br[C:41]1[N:46]=[C:45]([CH:47]2[CH2:49][CH2:48]2)[CH:44]=[CH:43][N:42]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>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]>[CH:47]1([C:45]2[CH:44]=[CH:43][N:42]=[C:41]([C:9]3[C:17]4[C:12](=[CH:13][CH:14]=[C:15]([C:18]5[O:22][C:21]([NH:23][CH2:24][C:25]([F:27])([F:26])[F:28])=[N:20][N:19]=5)[CH:16]=4)[N:11]([S:29]([C:32]4[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=4)(=[O:31])=[O:30])[CH:10]=3)[N:46]=2)[CH2:49][CH2:48]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 49758247HCID 49758247, compoundHCID 683280655-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine

Product 1

HCID 683285315-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

To a 5 mL glass microwave tube containing 5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine (180 mg, 0.320 mmol) was added 2-bromo-4-cyclopropylpyrimidine (73.3 mg, 0.368 mmol) (CombiPhos Catalysts Inc.), potassium phosphate (204 mg, 0.960 mmol) (Sigma-Aldrich), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (9.16 mg, 0.019 mmol) (Strem), and Pd2(dba)3 (8.79 mg, 9.60 μmol) (Strem). The tube was purged with argon, the solids were treated with dioxane (2.0 mL) and water (0.200 mL), the tube was sealed, and the contents were heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 20 min. The mixture was treated with H2O and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by flash chromatography (20-100% EtOAc in Hex) affording 5-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine as an amorphous beige solid. MS (ESI, pos. ion) m/z: 554.9 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.03 (s, 1H), 8.63-8.71 (m, 2H), 8.53 (s, 1H), 8.16 (d, J=8.8 Hz, 1H), 8.04 (m, J=8.4 Hz, 2H), 7.92 (d, J=7.2 Hz, 1H), 7.43 (m, J=8.2 Hz, 2H), 7.37 (d, J=5.1 Hz, 1H), 4.06-4.21 (m, 2H), 2.33 (s, 3H), 2.16-2.27 (m, 1H), 1.24 (br. s., 2H), 1.18 (d, J=6.7 Hz, 2H).

Workup

  1. customThe tube was purged with argon
  2. additionthe solids were treated with dioxane (2.0 mL) and water (0.200 mL)
  3. customthe tube was sealed
  4. additionThe mixture was treated with H2O
  5. extractionextracted with EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by flash chromatography (20-100% EtOAc in Hex)

Sources & evidence

ORD record
ord-40a540e109564bb4ac20bc7d8c0e7903
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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