Cesium carbonate → HCID 67050703, compound

HRID 1498571Notes

Reaction equation

HRID 1498571 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.Cl.C([O:29][C:30](=[O:34])[C@H:31]([CH3:33])[NH2:32])(C)(C)C.F[B-](F)(F)F.Cl.C(C1NC=C[N+]=1C(C)C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC>[CH:19]([N:18]1[C:14]([C:12]2[N:13]=[C:6]3[N:7]([CH2:8][CH2:9][O:10][C:4]4[CH:3]=[C:2]([NH:32][C@@H:31]([CH3:33])[C:30]([OH:34])=[O:29])[CH:23]=[CH:22][C:5]=43)[CH:11]=2)=[N:15][CH:16]=[N:17]1)([CH3:21])[CH3:20]

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 26255TetrafluoroborateHCID 11275390tert-Butyl alaninate hydrochlorideHCID 582043138-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azuleneHCID 67050716HCID 67050716, compound

Product 1

HCID 67050703HCID 67050703, compoundYield 41.8%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 8-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene 194 (0.72 g, 1.69 mmol), alanine tert-butyl ester hydrochloride (1.52 g, 8.4 mmol), Rh(COD)2.BF4 (0.07 g, 0.18 mmol), diisopropylimidazolium hydrochloride (0.07 g, 0.35 mmol) and cesium carbonate (4.38 g, 13.4 mmol) in DME (7 mL) was heated at 90° C. under an argon atmosphere for 16 h. The reaction mixture was concentrated in vacuo and the resultant residue partitioned between DCM and water. The aqueous phase was acidified with 1M HCl, extracted with 10% methanol in DCM and the combined organic extracts dried (Na2SO4) and concentrated in vacuo to give (S)-2-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-ylamino]-propionic acid (0.27 g, 33%). LCMS: RT=2.47 min, [M+H]+=383.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe resultant residue partitioned between DCM and water
  3. extractionextracted with 10% methanol in DCM
  4. dry with materialthe combined organic extracts dried (Na2SO4)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-48ab9a4868474ffe9708911d36614f78
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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