Hydrochloric Acid → HCID 58204628, compound

HRID 886184Notes

Reaction equation

HRID 886184 reaction equation
Br[C:2]1[CH:23]=[CH:22][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:19]([CH3:21])[CH3:20])[N:16]=[CH:17][N:18]=1)[N:7]=3.C([O-])(=O)C.[K+].O1CCCCC1[O:35][CH2:36][CH2:37][N:38]1[CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:40]=[N:39]1.Cl>CC#N.CCOC(C)=O.O.C(Cl)Cl.O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:19]([N:15]1[C:14]([C:8]2[N:7]=[C:6]3[C:5]4[CH:22]=[CH:23][C:2]([C:41]5[CH:40]=[N:39][N:38]([CH2:37][CH2:36][OH:35])[CH:42]=5)=[CH:3][C:4]=4[O:13][CH2:12][CH2:11][N:10]3[CH:9]=2)=[N:18][CH:17]=[N:16]1)([CH3:21])[CH3:20]

Participants

11

Reactant 4

HCID 313Hydrochloric AcidHCID 517044Potassium AcetateHCID 582043138-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azuleneHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 58204628HCID 58204628, compoundYield 74%

Reagents, catalysts & solvents 6

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a 10-mL microwave vial was added 9-bromo-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine 194 (0.210 g, 0.56 mmol) and potassium acetate (0.17 g, 1.68 mmol), MeCN (1 mL) and water (2 mL). The mixture was thoroughly purged with N2. A solution of 1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.271 g, 0.84 mmol) in MeCN (1 mL) was added, followed by tetrakis(triphenylphosphine) palladium (65 mg, 0.056 mmol) and the vial was sealed immediately. The mixture was irradiated with microwave at 150° C. for 20 minutes. Complete conversion was observed by LC/MS (a small amount of des-THP product was observed). The reaction mixture was diluted with EtOAc and water and extracted three times with EtOAc. The organic phases were combined, dried with MgSO4 and concentrated. The residue was purified using ISCO chromatography using 10% MeOH/EtOAc, which gave 170 mg, 0.35 mmol (62%) a white foaming solid as product which was immediately dissolved in DCM (2 mL) and treated with 4 M hydrogen chloride in 1,4-dioxane (0.35 mL). A white precipitate developed during the addition. The reaction was stirred at room temperature for 1 h. The reaction mixture was concentrated to dryness and dissolved in DMF/H2O. This mixture was purified by rp-HPLC to provide 105 mg (74% yield) of 182 as a white, partially crystalline solid. LS/MS (ESI+): m/z 406 (M+H). 1H NMR (400 MHz, DMSO) δ 8.37 (d, J=8.4, 1H), 8.22 (s, 1H), 7.95 (s, 1H), 7.91 (s, 2H), 7.38 (dd, J=8.4, 1.8, 1H), 7.27 (d, J=1.7, 1H), 5.91 (dq, J=13.3, 6.7, 1H), 4.91 (t, J=5.3, 1H), 4.58-4.44 (m, 4H), 4.16 (t, J=5.6, 2H), 3.77 (q, J=5.4, 2H), 1.49 (d, J=6.6, 6H)

Workup

  1. customThe mixture was thoroughly purged with N2
  2. customthe vial was sealed immediately
  3. customThe mixture was irradiated with microwave at 150° C. for 20 minutes
  4. extractionextracted three times with EtOAc
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified
  8. customgave 170 mg, 0.35 mmol (62%) a white foaming solid as product which
  9. additionA white precipitate developed during the addition
  10. concentrationThe reaction mixture was concentrated to dryness
  11. dissolutiondissolved in DMF/H2O
  12. customThis mixture was purified by rp-HPLC

Sources & evidence

ORD record
ord-cd8b4f9717fa4428b2f4e5da4771b8a5
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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