Water → 1-(4-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1-methyl-1H-imidazol-2-yl)-2-methylpropan-2-ol

HRID 1800097Notes

Reaction equation

HRID 1800097 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[CH:19][C:20](B5OC(C)(C)C(C)(C)O5)=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:31]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].Br[C:33]1[N:34]=[C:35]([CH2:39][C:40]([CH3:43])([OH:42])[CH3:41])[N:36]([CH3:38])[CH:37]=1.[F-].[Cs+].O>CN(C=O)C.[Cu]I.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:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[CH:19][C:20]([C:33]5[N:34]=[C:35]([CH2:39][C:40]([CH3:43])([OH:42])[CH3:41])[N:36]([CH3:38])[CH:37]=5)=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:31]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 962WaterHCID 25953Cesium fluorideHCID 582047132-(1-isopropyl-1H-1,2,4-triazol-5-yl)-9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineHCID 670506471-(4-bromo-1-methyl-1H-imidazol-2-yl)-2-methyl-propan-2-ol

Product 1

HCID 582044021-(4-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1-methyl-1H-imidazol-2-yl)-2-methylpropan-2-olYield 16.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a mixture of 2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (200 mg, 0.48 mmol) and 1-(4-bromo-1-methyl-1H-imidazol-2-yl)-2-methyl-propan-2-ol (166 mg, 0.71 mmol) in dry DMF (2 mL) under nitrogen was added CsF (180 mg, 1.19 mmol), CuI (9 mg, 0.048 mmol) and Pd(PPh3)4 (27 mg, 0.024 mmol). The reaction mixture was heated at 130° C. for 40 min under microwave. Cooled to room temperature, the resulting mixture was poured into water and extracted with EtOAc. Dried organics over sodium sulfate and purified by pre-HPLC to give 272 as a white solid (34.9 mg, yield: 16%). 1H NMR (DMSO-d6, 400 MHz): δ8.51 (s, 1H), 7.90 (s, 1H), 7.86 (s, 1H), 7.23-7.11 (m, 3H), 5.93-5.89 (m, 1H), 4.54-4.52 (m, 4H), 3.74-3.66 (m, 5H), 1.46 (dd, J=6.4 Hz, 6H), 1.24 (brs, 6H). MS: (ESI, m/z)=448 [M+H]+

Workup

  1. temperatureCooled to room temperature
  2. extractionextracted with EtOAc
  3. customDried organics over sodium sulfate and purified by pre-HPLC

Sources & evidence

ORD record
ord-3afa7f86a4a244c39e675ac092f5f431
Source dataset
uspto-grants-2013_01
Patent number
US08343955B2

Reaction notes

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