Tetramethyltin → 7-methyl-6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-propyl]-amide

HRID 926405Notes

Reaction equation

HRID 926405 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[N:8]=[CH:7][C:6]([C@H:9]([NH:12][C:13]([C:15]2[C:16](Br)=[C:17]([C:24]([N:26]3[CH2:30][CH2:29][CH2:28][C@@H:27]3[CH3:31])=[O:25])[N:18]3[CH2:23][CH2:22][O:21][CH2:20][C:19]=23)=[O:14])[CH2:10][CH3:11])=[CH:5][CH:4]=1.[CH3:35][Sn](C)(C)C>CN(C)C=O.C1(P([Pd-4](P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:1][C:2]([F:34])([F:33])[C:3]1[N:8]=[CH:7][C:6]([C@H:9]([NH:12][C:13]([C:15]2[C:16]([CH3:35])=[C:17]([C:24]([N:26]3[CH2:30][CH2:29][CH2:28][C@@H:27]3[CH3:31])=[O:25])[N:18]3[CH2:23][CH2:22][O:21][CH2:20][C:19]=23)=[O:14])[CH2:10][CH3:11])=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 11661TetramethyltinHCID 897341547-bromo-6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-propyl]-amide

Product 1

HCID 897339607-methyl-6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-propyl]-amideYield 92%

Reagents, catalysts & solvents 2

HCID 178420553HCID 178420553, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 7-bromo-6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-propyl]-amide (Comp. No. 16ru) (55 mg, 0.101 mmol), tetramethylstannane (101 mg, 0.57 mmol) and tetrakis(triphenylphosphino)palladium(0) (6 mg, 5 pmol) in dimethylformamide (2 ml) was heated at 110° C. under microwave irradiation for 1 h. The crude product was purified by reverse phase HPLC to give 45 mg (92%) of 7-methyl-6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-propyl]-amide. LC/MS (method 3): Rt=1.85 min; m/z=479.32 (M+H+).

Workup

  1. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-70d5f217bc6742e5820b66483e7abcf6
Source dataset
uspto-grants-2016_03
Patent number
US09284333B2

Reaction notes

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