9-Bromo-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine → HCID 68313219, compound

HRID 1530645Notes

Reaction equation

HRID 1530645 reaction equation
Br[C:2]1[CH:24]=[CH:23][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[N:18]([CH:19]([CH3:21])[CH3:20])[N:17]=[C:16]([CH3:22])[N:15]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.Cl.[NH:26]1[CH2:30][CH2:29][CH2:28][CH:27]1[CH:31]1[CH2:36][CH2:35][N:34]([CH:37]2[CH2:42][CH2:41][O:40][CH2:39][CH2:38]2)[CH2:33][CH2:32]1>C1(C)C=CC=CC=1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:19]([N:18]1[C:14]([C:12]2[N:13]=[C:6]3[C:5]4[CH:23]=[CH:24][C:2]([N:26]5[CH2:30][CH2:29][CH2:28][CH:27]5[CH:31]5[CH2:36][CH2:35][N:34]([CH:37]6[CH2:42][CH2:41][O:40][CH2:39][CH2:38]6)[CH2:33][CH2:32]5)=[CH:3][C:4]=4[O:10][CH2:9][CH2:8][N:7]3[CH:11]=2)=[N:15][C:16]([CH3:22])=[N:17]1)([CH3:21])[CH3:20]

Participants

5

Reactant 2

HCID 582043229-Bromo-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineHCID 68313202HCID 68313202, compound

Product 1

HCID 68313219HCID 68313219, compoundYield 4.6%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 9-bromo-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (200 mg, 0.516 mmol), 4-(pyrrolidin-2-yl)-1-(tetrahydro-2H-pyran-4-yl)piperidine hydrochloride (354 mg, 1.29 mmol), Pd(PtBu3)2 (20 mg, 0.04 mmol), Na2OtBu (148 mg, 1.55 mmol) in toluene (5.0 ml) in a seal tube was degassed with N2 for three times. The mixture was stirred at 110° C. for 120 min. The solid was filtered through Celite. The filtrate was concentrated to give the crude product, which was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/1% formic acid, 17 min) to give racemic 254 (13 mg, 4.6% yield). LCMS (ESI): RT=2.00 min, m/z: 546.4 [M+H+]. 1H NMR (500 MHz, CDCl3): δ 8.33 (d, J=8.5 Hz, 1H), 7.53 (s, 1H), 6.47 (dd, J=9.5 Hz, 2.5 Hz, 1H), 6.18 (d, J=2.5 Hz, 1H), 5.95-5.92 (m, 1H), 4.48-4.36 (m, 4H), 4.05 (d, J=8.5 Hz, 1H), 3.85-3.75 (m, 1H), 3.41-3.24 (m, 6H), 2.41 (s, 4H), 2.02-1.74 (m, 14H), 1.56 (d, J=6.5 Hz, 7H)

Workup

  1. customwas degassed with N2 for three times
  2. filtrationThe solid was filtered through Celite
  3. concentrationThe filtrate was concentrated
  4. customto give the crude product, which
  5. customwas purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/1% formic acid, 17 min)

Sources & evidence

ORD record
ord-c639307e8a6f4aa49a8764bfb9e8064a
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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