Acetonitrile → 2-Methyl-1-(4-{2-[1-(2,2,2-trifluoro-ethyl)-1H-imidazol-2-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl}-pyrazol-1-yl)-propan-2-ol

HRID 708104Notes

Reaction equation

HRID 708104 reaction equation
Br[C:2]1[CH:25]=[CH:24][C:5]2[C:6]3[N:7]=[C:8]([C:14]4[N:15]([CH2:19][C:20]([F:23])([F:22])[F:21])[CH:16]=[CH:17][N:18]=4)[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1.C(#N)C.C(=O)([O-])[O-].[K+].[K+].[CH3:35][C:36]([OH:53])([CH3:52])[CH2:37][N:38]1[CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:40]=[N:39]1>O.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>[CH3:35][C:36]([OH:53])([CH3:52])[CH2:37][N:38]1[CH:42]=[C:41]([C:2]2[CH:25]=[CH:24][C:5]3[C:6]4[N:7]=[C:8]([C:14]5[N:15]([CH2:19][C:20]([F:23])([F:21])[F:22])[CH:16]=[CH:17][N:18]=5)[S:9][C:10]=4[CH2:11][CH2:12][O:13][C:4]=3[CH:3]=2)[CH:40]=[N:39]1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 582041312-methyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-2-olHCID 670506488-Bromo-2-[1-(2,2,2-trifluoro-ethyl)-1H-imidazol-2-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

Product 1

HCID 582040352-Methyl-1-(4-{2-[1-(2,2,2-trifluoro-ethyl)-1H-imidazol-2-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl}-pyrazol-1-yl)-propan-2-ol

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

8-Bromo-2-[1-(2,2,2-trifluoro-ethyl)-1H-imidazol-2-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (110.0 mg, 0.2557 mmol) dissolved in Acetonitrile (0.534 mL, 10.2 mmol) and with dissolved 2.00 M of Potassium carbonate in Water (0.256 mL). Degas by bubbling nitrogen for 5 min. The reaction was charged with 2-methyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propan-2-ol (102 mg, 0.384 mmol) then Tetrakis(triphenylphosphine)palladium(0) (41.36 mg, 0.03579 mmol). The reaction was heated in microwave at 140 C for 10 min. The reaction was cooled to r.t. then extracted with ethyl acetate. Combined organics concentrated and purified by reverse phase HPLC to give 355. MS: (ESI+)=490.1. 1H NMR (400 MHz, DMSO) δ 8.24 (d, J=8.3 Hz, 1H), 8.17 (s, 1H), 7.95 (s, 1H), 7.55 (s, 1H), 7.41 (dd, J=8.3, 1.8 Hz, 1H), 7.29 (d, J=1.8 Hz, 1H), 7.18 (d, J=1.2 Hz, 1H), 5.74 (q, J=8.9 Hz, 2H), 4.71 (s, 1H), 4.37 (t, J=5.0 Hz, 2H), 4.03 (s, 2H), 3.40 (t, J=5.0 Hz, 2H), 1.09 (s, 6H)

Workup

  1. customDegas
  2. customby bubbling nitrogen for 5 min
  3. temperatureThe reaction was heated in microwave at 140 C for 10 min
  4. extractionthen extracted with ethyl acetate
  5. concentrationCombined organics concentrated
  6. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-8eee6f8621784097b10b155a69854b86
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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