Potassium Carbonate → 3-(2-Carbamoyl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-9-ylethynyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 575072Notes

Reaction equation

HRID 575072 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.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].[C:54]([O:58][C:59]([N:61]1[CH2:65][CH2:64][C:63]([C:67]#[CH:68])([OH:66])[CH2:62]1)=[O:60])([CH3:57])([CH3:56])[CH3:55]>CN(C)C=O.CC([O-])=O.CC([O-])=O.[Pd+2].[Cu]I>[C:15]([C:9]1[N:8]=[C:7]2[C:6]3[CH:18]=[C:2]([C:68]#[C:67][C:63]4([OH:66])[CH2:64][CH2:65][N:61]([C:59]([O:58][C:54]([CH3:56])([CH3:55])[CH3:57])=[O:60])[CH2:62]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

8

Reactant 4

HCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 18366064Tert-butyl 3-ethynyl-3-hydroxypyrrolidine-1-carboxylateHCID 6831288310-Bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

Product 1

HCID 866931003-(2-Carbamoyl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-9-ylethynyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl esterYield 28.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

This compound was prepared according to a procedure similar to that described in Procedure H. In a solution of 9-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide (100 mg, 0.32 mmol) in N,N-Dimethyl-formamide (3 mL) were added 1,3-bis(diphenylphosphino)-propane (26 mg, 0.064 mmol), Pd(OAc)2 (7.2 mg, 0.032 mmol), K2CO3 (110 mg, 0.8 mmol), 3-Ethynyl-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (136 mg, 0.64 mmol) and CuI (12 mg, 0.064 mmol). Then the solution was bubbled N2 for 5 min and microwaved for 1 h at 120° C. under nitrogen. The reaction mixture was filtrated and the filtrate was purified by column to afford crude titled compound (40 mg, 28%). LCMS=383.0 [M-56]+.

Workup

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

Sources & evidence

ORD record
ord-bf77705285c54988aba1c26ab0cd3862
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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