Potassium Phosphate, Tribasic → 2-(5-(9-cyclopropyl-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-2-yl)-3-methyl-1H-1,2,4-triazol-1-yl)propan-1-ol

HRID 1800096Notes

Reaction equation

HRID 1800096 reaction equation
Br[C:2]1[CH:25]=[CH:24][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:18]([CH:19]([CH3:22])[CH2:20][OH:21])[N:17]=[C:16]([CH3:23])[N:15]=1)[N:7]=3.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:34]1(B2OC(C)(C)C(C)(C)O2)[CH2:36][CH2:35]1>O1CCCC1.O.C(Cl)Cl.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>[CH:34]1([C:2]2[CH:25]=[CH:24][C:5]3[C:6]4[N:10]([CH:9]=[C:8]([C:14]5[N:18]([CH:19]([CH3:22])[CH2:20][OH:21])[N:17]=[C:16]([CH3:23])[N:15]=5)[N:7]=4)[CH2:11][CH2:12][O:13][C:4]=3[CH:3]=2)[CH2:36][CH2:35]1

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27580152-Cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 67050760HCID 67050760, compound

Product 1

HCID 582047682-(5-(9-cyclopropyl-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-2-yl)-3-methyl-1H-1,2,4-triazol-1-yl)propan-1-olYield 27.7%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with a solution of 2-[5-(8-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-2-yl)-3-methyl-[1,2,4]triazol-1-yl]-propan-1-ol (0.140 g, 0.000346 mol) and Potassium phosphate (0.220 g, 0.00104 mol) in Tetrahydrofuran (2.0 mL) and Water (2.0 mL). The mixture was thoroughly purged with N2. 2-cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.189 mL, 0.00104 mol) and Tetrakis(triphenylphosphine)palladium(0) (0.0400 g, 0.0000346 mol) were added and the vial was sealed immediately. The reaction was heated in the microwave to 120° C. for 20 minutes. The reaction was diluted with methylene chloride and filtered through celite. Saturated NH4Cl was added and the mixture was extracted 3 times with methylene chloride. The organic layers were combined, dried with MgSO4 and concentrated. The crude was purified by reverse-phase HPLC to give 35 mg of 270 as a white solid. MS (ESI+) 366.2. 1H NMR (500 MHz, DMSO) δ 8.26 (d, J=8.3 Hz, 1H), 7.82 (s, 1H), 6.86 (dd, J=8.4, 1.7 Hz, 1H), 6.75 (d, J=1.7 Hz, 1H), 5.73-5.57 (m, 1H), 4.85 (t, J=5.4 Hz, 1H), 4.50-4.43 (m, 4H), 3.76 (ddd, J=10.7, 7.5, 6.0 Hz, 1H), 3.68-3.62 (m, 1H), 2.24 (s, 3H), 1.97-1.85 (m, 1H), 1.39 (d, J=6.7 Hz, 3H), 1.02-0.93 (m, 2H), 0.75-0.67 (m, 2H)

Workup

  1. customThe mixture was thoroughly purged with N2
  2. customthe vial was sealed immediately
  3. filtrationfiltered through celite
  4. additionSaturated NH4Cl was added
  5. extractionthe mixture was extracted 3 times with methylene chloride
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated
  8. customThe crude was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-771fb63810d74a11953624a2e5628531
Source dataset
uspto-grants-2013_01
Patent number
US08343955B2

Reaction notes

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