Triethylamine → 3-(4-Methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylmethylene)-azetidine-1-carboxylic acid tert-butyl ester

HRID 519017Notes

Reaction equation

HRID 519017 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[O:12][CH2:11][C:10]1[N:5]2[CH:6]([CH3:17])[C:7](=[O:16])[NH:8][N:9]=1.[C:18]([O:22][C:23]([N:25]1[CH2:28][C:27](=[CH2:29])[CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.C(N(CC)CC)C>CC#N.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:18]([O:22][C:23]([N:25]1[CH2:28][C:27](=[CH:29][C:2]2[CH:3]=[C:4]3[C:13](=[CH:14][CH:15]=2)[O:12][CH2:11][C:10]2[N:5]3[CH:6]([CH3:17])[C:7](=[O:16])[NH:8][N:9]=2)[CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 55269097tert-Butyl 3-methylideneazetidine-1-carboxylateHCID 867273756-Bromo-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

Product 1

HCID 867273743-(4-Methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylmethylene)-azetidine-1-carboxylic acid tert-butyl esterYield 52%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of 6-bromo-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Preparation #1, Step D, 0.30 g, 1.013 mmol), 3-methylene-azetidine-1-carboxylic acid tert-butyl ester (0.343 g, 2.026 mmol), Pd(OAc)2 (0.023 g, 0.101 mmol), tri-O-tolylphosphine (0.0617 g, 0.203 mmol) and triethylamine (0.308 mg, 3.04 mmol) in CH3CN (10 mL) was heated at 110° C. for 14 h. The mixture was cooled to ambient temperature and the solvent was removed in vacuo. The residue was purified by preparative TLC (eluting with 50% EtOAc in petroleum ether) to give 3-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylmethylene)-azetidine-1-carboxylic acid tert-butyl ester as yellow solid (0.201 g, 52%), which was used directly in the next step. LC/MS (Table 1, Method 2) Rt=1.264 min; MS m/z: 385 [M+H]+.

Workup

  1. customthe solvent was removed in vacuo
  2. customThe residue was purified by preparative TLC (eluting with 50% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-c7919728c9644d04a26ada6ce322b496
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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