Water → HCID 51355335, compound

HRID 1190335Notes

Reaction equation

HRID 1190335 reaction equation
C(OC(=O)[NH:7][C:8]1[N:12]=[C:11]([C:13]2[S:14][C:15]3[CH2:16][CH2:17][O:18][C:19]4[CH:26]=[C:25](Br)[CH:24]=[CH:23][C:20]=4[C:21]=3[N:22]=2)[N:10]([C:28]([CH3:31])([CH3:30])[CH3:29])[N:9]=1)(C)(C)C.O.C([O-])(=O)C.[K+].CC1(C)C(C)(C)OB([C:47]2[CH:48]=[N:49][NH:50][CH:51]=2)O1>CC#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:28]([N:10]1[C:11]([C:13]2[S:14][C:15]3[CH2:16][CH2:17][O:18][C:19]4[CH:26]=[C:25]([C:47]5[CH:48]=[N:49][NH:50][CH:51]=5)[CH:24]=[CH:23][C:20]=4[C:21]=3[N:22]=2)=[N:12][C:8]([NH2:7])=[N:9]1)([CH3:30])([CH3:31])[CH3:29]

Participants

7

Reactant 4

HCID 962WaterHCID 517044Potassium AcetateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58204169HCID 58204169, compound

Product 1

HCID 51355335HCID 51355335, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

[5-(8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-1-tert-butyl-1H-[1,2,4]triazol-3-yl]-carbamic acid tert-butyl ester (0.94 g, 1.8 mmol) was dissolved in MeCN (20 mL) and H2O (20 mL) and added potassium acetate (601 mg, 6.12 mmol). The reaction flask was degassed by bubbling N2 for 5 min. Charged with 4,4,5,5-tetramethyl-2-(1H-pyrazol-4-yl)-1,3,2-dioxaborolane (456 mg, 2.53 mmol) and then tetrakis(triphenylphosphine)palladium(0) (280 mg, 0.24 mmol). The reaction was subjected to microwave irradiation at 140° C. for 20 min. The reaction was cooled to r.t., filtered through a plug of Celite and diluted with water. Extracted three times with EtOAc and the combined organic portions were dried over MgSO4, filtered and concentrated. The crude residue was taken up in DCM (10 mL) and treated with trifluoroacetic acid (5 mL). Stirred at room temperature for 1 h and concentrated in vacuo. The resultant residue was taken up in a minimal amount of DMF/DMSO (1:1) and purified by rp-HPLC to provide 58 mg (10% yield) of 122. LC/MS (ESI+): m/z 408 (M+H). 1H NMR (400 MHz, DMSO) δ 12.96 (bs, 1H), 8.31 (m, 2H), 7.99 (bs, 1H), 7.50-7.39 (m, 2H), 7.34 (d, J=1.5, 2H), 5.47 (s, 2H), 4.47-4.24 (m, 4H), 3.39 (dd, J=15.8, 10.7, 4H), 1.78 (s, J=18.7, 9H).

Workup

  1. customThe reaction flask was degassed
  2. customby bubbling N2 for 5 min
  3. customirradiation at 140° C. for 20 min
  4. filtrationfiltered through a plug of Celite
  5. additiondiluted with water
  6. extractionExtracted three times with EtOAc
  7. dry with materialthe combined organic portions were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additiontreated with trifluoroacetic acid (5 mL)
  11. concentrationconcentrated in vacuo
  12. custompurified by rp-HPLC

Sources & evidence

ORD record
ord-d189cce6e2d2401d9ccb3418456268ad
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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