Potassium Phosphate, Tribasic → N-tert-butyl-5-(3-(5-fluoro-4-methoxypyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine

HRID 634231Notes

Reaction equation

HRID 634231 reaction equation
[C:1]([NH:5][C:6]1[O:7][C:8]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([S:20]([C:23]2[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH:15]=[C:14]3B2OC(C)(C)C(C)(C)O2)=[N:9][N:10]=1)([CH3:4])([CH3:3])[CH3:2].P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl[C:48]1[N:53]=[C:52]([O:54][CH3:55])[C:51]([F:56])=[CH:50][N:49]=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.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>[C:1]([NH:5][C:6]1[O:7][C:8]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([S:20]([C:23]2[CH:24]=[CH:25][C:26]([CH3:27])=[CH:28][CH:29]=2)(=[O:21])=[O:22])[CH:15]=[C:14]3[C:48]2[N:53]=[C:52]([O:54][CH3:55])[C:51]([F:56])=[CH:50][N:49]=2)=[N:9][N:10]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 135307042-Chloro-5-fluoro-4-methoxypyrimidineHCID 68328226HCID 68328226, compound

Product 1

HCID 68328407N-tert-butyl-5-(3-(5-fluoro-4-methoxypyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amineYield 60.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalyst

Conditions

Temperature
130 °C

Procedure

N-tert-Butyl-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 (166 mg, 0.309 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (6.63 mg, 0.014 mmol) (Strem), Pd2(dba)3 (6.37 mg, 6.96 μmol) (Strem), potassium phosphate (148 mg, 0.696 mmol) (Sigma-Aldrich) and 2-chloro-5-fluoro-4-methoxypyrimidine (37.7 mg, 0.232 mmol) were weighed into a 5 mL glass microwave tube. The tube was purged with argon and the solids were treated with dioxane (2 mL) and water (0.200 mL). The tube was sealed, and the contents were heated an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 130° 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 (eluting with 5-60% EtOAc in Hex) to give N-tert-butyl-5-(3-(5-fluoro-4-methoxypyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (75.5 mg, 0.141 mmol, 60.7%) as an off white solid. MS (ESI, pos. ion) m/z: 537.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.98-9.03 (m, 1H), 8.72 (d, J=3.1 Hz, 1H), 8.56 (s, 1H), 8.16 (d, J=8.8 Hz, 1H), 8.02-8.07 (m, 2H), 7.86-7.92 (m, 1H), 7.64 (s, 1H), 7.40-7.48 (m, 2H), 4.22 (s, 3H), 2.33 (s, 3H), 1.35-1.41 (m, 9H).

Workup

  1. customThe tube was purged with argon
  2. additionthe solids were treated with dioxane (2 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 (eluting with 5-60% EtOAc in Hex)

Sources & evidence

ORD record
ord-4461bb379d7d4696af5845a41d872b84
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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