Potassium Phosphate, Tribasic → HCID 68328004, compound

HRID 634307Notes

Reaction equation

HRID 634307 reaction equation
[CH:1]([NH:4][C:5]1[O:6][C:7]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15]([S:19]([C:22]2[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH:14]=[C:13]3B2OC(C)(C)C(C)(C)O2)=[N:8][N:9]=1)([CH3:3])[CH3:2].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Cl[C:73]1[N:78]=[C:77]([CH:79]2[CH2:81][CH2:80]2)[C:76]([C:82]([O:84][CH3:85])=[O:83])=[CH:75][N:74]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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:79]1([C:77]2[C:76]([C:82]([O:84][CH3:85])=[O:83])=[CH:75][N:74]=[C:73]([C:13]3[C:12]4[C:16](=[CH:17][CH:18]=[C:10]([C:7]5[O:6][C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[N:9][N:8]=5)[CH:11]=4)[N:15]([S:19]([C:22]4[CH:23]=[CH:24][C:25]([CH3:26])=[CH:27][CH:28]=4)(=[O:20])=[O:21])[CH:14]=3)[N:78]=2)[CH2:80][CH2:81]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 68328163HCID 68328163, compoundHCID 83835308Methyl 2-chloro-4-cyclopropylpyrimidine-5-carboxylate

Product 1

HCID 68328004HCID 68328004, compoundYield 40.3%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
130 °C

Procedure

A 20 mL microwave vial was charged with N-isopropyl-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 (300 mg, 0.574 mmol), Xphos (Stem Chemicals, Newburyport, Mass., 16.4 mg, 0.034 mmol), Pd2(dba)3 (Strem Chemicals, Newburyport, Mass., 15.8 mg, 0.017 mmol), methyl 2-chloro-4-cyclopropylpyrimidine-5-carboxylate (147 mg, 0.689 mmol) and potassium phosphate (366 mg, 1.723 mmol) followed by purging with argon. The solids were treated with dioxane (3 mL) and water (1.0 mL) and heated in the microwave at 130° C. for 20 min. The reaction mixture was treated with water and extracted with EtOAc, dried over MgSO4, filtered and concentrated. Purification of the crude residue on the ISCO (12 g Redisep column, using a gradient of 0-100% EtOAc in hexanes) afforded methyl 4-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1-tosyl-1H-indol-3-yl)pyrimidine-5-carboxylate (132.4 mg, 0.231 mmol, 40.3% yield) as light yellow amorphous solid. MS (ESI, pos. ion) m/z: 573.2 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 9.11 (1H, s), 9.04 (1H, d, J=1.2 Hz), 8.59 (1H, s), 8.08 (1H, d, J=8.8 Hz), 8.01 (1H, dd, J=8.8, 1.6 Hz), 7.86 (2H, d, J=8.4 Hz), 7.28 (2H, s), 4.55 (1H, br. s.), 4.00-4.08 (1H, m), 3.98 (3H, s), 3.24-3.34 (1H, m), 2.36 (3H, s), 1.32-1.39 (6H, m), 1.21-1.30 (4H, m).

Workup

  1. customby purging with argon
  2. additionThe solids were treated with dioxane (3 mL) and water (1.0 mL)
  3. additionThe reaction mixture was treated with water
  4. extractionextracted with EtOAc
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the crude residue on the ISCO (12 g Redisep column

Sources & evidence

ORD record
ord-ab7f24d6fc9342179b5536322a81867a
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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