Bromide ion → HCID 58204577, compound

HRID 1629417Notes

Reaction equation

HRID 1629417 reaction equation
Br[C:2]1[CH:23]=[CH:22][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]=[CH:16][N:15]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.[C:24]([O:28][C:29](=[O:35])[C@@H:30]1[CH2:34][CH2:33][CH2:32][NH:31]1)([CH3:27])([CH3:26])[CH3:25].CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1.[Br-]>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:22]=[CH:23][C:2]([N:31]5[CH2:32][CH2:33][CH2:34][C@H:30]5[C:29]([O:28][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:35])=[CH:3][C:4]=4[O:10][CH2:9][CH2:8][N:7]3[CH:11]=2)=[N:15][CH:16]=[N:17]1)([CH3:21])[CH3:20]

Participants

7

Reactant 5

HCID 259Bromide ionHCID 1140TolueneHCID 6453108L-Proline 1,1-dimethylethyl ester2×HCID 23676156Sodium t-butoxide2×HCID 582043138-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

Product 1

HCID 58204577HCID 58204577, compound

Reagents, catalysts & solvents 1

HCID 178418851HCID 178418851, compoundCatalyst

Conditions

Temperature
95 °C

Procedure

A degassed mixture of 374 mg, (1.00 mmol) of 9-bromo-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine 194, 342.5 mg, (2.000 mmol) of L-Proline tert-Butyl Ester, 26 mg, (0.050 mmol) of Bis(tri-t-butylphosphine)palladium and 192 mg, (2.00 mmol) of Sodium tert-butoxide in Toluene (10.0 mL, 93.9 mmol) was heated at 95° C. for 24 hours. The same quantity of L-Proline tert-Butyl Ester, Sodium tert-butoxide and the catalyst were added and the mixture was heated for 6 hours at 115° C. until no starting bromide remains in the reaction mixture. The mixture was concentrated in vacuum, the residue distributed between ethyl acetate and 5% aqueous citric acid. The organic extracts were washed with water, sat. NaHCO3, water, brine, dried over MgSO4 and purified on a silicagel 12 g column eluting with 4% Methanol in DCM to give (S)-tert-butyl 1-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)pyrrolidine-2-carboxylate. Yield 153 mg (55-60% purity, the product is contaminated with debromination byproduct). M/z 465.2, calc. 464.25

Workup

  1. concentrationThe mixture was concentrated in vacuum
  2. washThe organic extracts were washed with water, sat. NaHCO3, water, brine
  3. dry with materialdried over MgSO4
  4. custompurified on a silicagel 12 g column
  5. washeluting with 4% Methanol in DCM

Sources & evidence

ORD record
ord-9dc2d7aeed714e3cb84062632f1d6b6d
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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