1,4-Dioxane → N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepin-10-amine

HRID 1498326Notes

Reaction equation

HRID 1498326 reaction equation
Cl[C:2]1[N:12]=[CH:11][C:10]2[O:9][CH2:8][CH2:7][N:6]3[CH:13]=[C:14]([C:16]4[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[CH:18][N:17]=4)[N:15]=[C:5]3[C:4]=2[CH:3]=1.[CH3:24][C:25]1([CH3:32])[O:29][CH:28]([CH2:30][NH2:31])[CH2:27][O:26]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+].O1CCOCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:24][C:25]1([CH3:32])[O:29][CH:28]([CH2:30][NH:31][C:2]2[N:12]=[CH:11][C:10]3[O:9][CH2:8][CH2:7][N:6]4[CH:13]=[C:14]([C:16]5[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[CH:18][N:17]=5)[N:15]=[C:5]4[C:4]=3[CH:3]=2)[CH2:27][O:26]1

Participants

7

Reactant 5

HCID 312751,4-DioxaneHCID 41223491,3-Dioxolane-4-methanamine, 2,2-dimethyl-HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 5820431910-chloro-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepine

Product 1

HCID 67050685N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepin-10-amine

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

A solution of 10-chloro-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepine (90.0 mg, 0.272 mmol), (2,2-dimethyl-1,3-dioxolan-4-yl)methanamine (0.0353 mL, 0.272 mmol), Palladium Acetate (6.11 mg, 0.0272 mmol), XPhos (13.0 mg, 0.0272 mmol), and Sodium-tert-butoxide (52.3 mg, 0.544 mmol) in 1,4-Dioxane (1.50 mL, 19.2 mmol) was heated in microwave at 115° C. for 20 min. The reaction was filtered thru celite then rinsed with EtOAc. The filtrate was washed water, brine. The organic layer was dried Na2SO4, concentrated to give intermediate N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepin-10-amine to which was added 4.00 M of Hydrogen chloride in dioxane (5.00 mL). The reaction was stirred 3 h. The reaction was concentrated and submitted HPLC purification to give 262. MS: (ESI+)=386.2. 1H NMR (500 MHz, DMSO) δ 7.99 (s, 1H), 7.92 (s, 1H), 7.85 (s, 1H), 7.44 (s, 1H), 6.36 (s, 1H), 5.86 (dt, J=13.2, 6.6 Hz, 1H), 4.78 (d, J=4.8 Hz, 1H), 4.61-4.46 (m, 3H), 4.46-4.33 (m, 2H), 3.64 (dd, J=11.4, 5.3 Hz, 1H), 3.47-3.34 (m, 3H), 3.21-3.10 (m, 1H), 1.49 (d, J=6.6 Hz, 6H)

Workup

  1. filtrationThe reaction was filtered thru celite
  2. washthen rinsed with EtOAc
  3. washThe filtrate was washed water, brine
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-b7510e5a518f49968ce332f256af7243
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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