Dichloromethane → 3-methyl-3-((R)-1-methyl-2-oxo-8-vinyl-1,2,3,5-tetrahydro-6-oxa-3,4,10,11 b-tetraaza-cyclopenta[b]phenanthren-10-yl)-azetidine-1-carboxylic acid tert-butyl ester

HRID 519143Notes

Reaction equation

HRID 519143 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([N:13]2[C:29]3[C:16](=[CH:17][C:18]4[O:19][CH2:20][C:21]5[N:26]([C:27]=4[CH:28]=3)[C@H:25]([CH3:30])[C:24](=[O:31])[NH:23][N:22]=5)[C:15](I)=[CH:14]2)([CH3:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:33][C:34]1(C)C(C)(C)OB(C=C)O1.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([CH3:12])([N:13]2[C:29]3[C:16](=[CH:17][C:18]4[O:19][CH2:20][C:21]5[N:26]([C:27]=4[CH:28]=3)[C@H:25]([CH3:30])[C:24](=[O:31])[NH:23][N:22]=5)[C:15]([CH:33]=[CH2:34])=[CH:14]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 867275343-((R)-8-iodo-1-methyl-2-oxo-1,2,3,5-tetrahydro-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-10-yl)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 867275353-methyl-3-((R)-1-methyl-2-oxo-8-vinyl-1,2,3,5-tetrahydro-6-oxa-3,4,10,11 b-tetraaza-cyclopenta[b]phenanthren-10-yl)-azetidine-1-carboxylic acid tert-butyl esterYield 90%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3-((R)-8-iodo-1-methyl-2-oxo-1,2,3,5-tetrahydro-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-10-yl)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.3 g, 0.544 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.838 g, 5.44 mmol), K2CO3 (0.15 g, 1.088 mmol) and Pd(dppf)Cl2.CH2Cl2 (0.044 g, 0.054 mmol) in dioxane (6 mL) and water (1 mL) was heated at 68° C. for 14 h. The reaction mixture was cooled to ambient temperature and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (eluting with 10%˜100% EtOAc in petroleum ether) to give 3-methyl-3-((R)-1-methyl-2-oxo-8-vinyl-1,2,3,5-tetrahydro-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-10-yl)-azetidine-1-carboxylic acid tert-butyl ester (0.22 g, 90%) as yellow gum, which was used directly in the next step. LC/MS (Table 1, Method 25) Rt=0.892 min.; MS m/z: 452 [M+H]+.

Workup

  1. customthe solvent was removed in vacuo
  2. customThe residue was purified by column chromatography on silica gel (eluting with 10%˜100% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-3f211594d21a48e3ac72b8a937dce078
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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