10-Bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide → 3-(2-Carbamoyl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-9-ylethynyl)-3-hydroxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester

HRID 575075Notes

Reaction equation

HRID 575075 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([C:15]([NH2:17])=[O:16])=[CH:10]3)[C:6]=2[CH:18]=1.[C:19]([O:23][C:24]([N:26]1[CH:31]2[CH2:32][CH2:33][CH:27]1[CH2:28][C:29]([C:35]#[CH:36])([OH:34])[CH2:30]2)=[O:25])([CH3:22])([CH3:21])[CH3:20]>C(#N)C.C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:15]([C:9]1[N:8]=[C:7]2[C:6]3[CH:18]=[C:2]([C:36]#[C:35][C:29]4([OH:34])[CH2:30][CH:31]5[N:26]([C:24]([O:23][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:25])[CH:27]([CH2:33][CH2:32]5)[CH2:28]4)[CH:3]=[CH:4][C:5]=3[O:14][CH2:13][CH2:12][N:11]2[CH:10]=1)(=[O:16])[NH2:17]

Participants

7

Reactant 2

HCID 6831288310-Bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamideHCID 866930923-Ethynyl-3-hydroxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester

Product 1

HCID 866931023-(2-Carbamoyl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-9-ylethynyl)-3-hydroxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl esterYield 104.5%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

This compound was prepared according to a procedure similar to that described in Procedure E. In a solution of 9-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide (300 mg, 1.0 mmol) in acetonitrile (6 mL) and triethylamine (3 mL) were added Pd(PPh3)2Cl2 (70 mg, 0.1 mmol), 3-Ethynyl-3-hydroxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.5 g, 2 mmol) and CuI (19 mg, 0.1 mmol). Then the solution was bubbled N2 for 5 min and microwaved for 2 h at 120° C. under nitrogen. The reaction mixture was filtered and the filtrate was purified by column (EtOAc/hexanes 2:1) to afford crude product (0.5 g, 99%). LCMS=479.2 [M+H]+.

Workup

  1. customThis compound was prepared
  2. customThen the solution was bubbled N2 for 5 min
  3. custommicrowaved for 2 h at 120° C. under nitrogen
  4. filtrationThe reaction mixture was filtered
  5. customthe filtrate was purified by column (EtOAc/hexanes 2:1)

Sources & evidence

ORD record
ord-b29427394ab64ebe914fe38ead97ad51
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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