1,4-Dioxane → (S)-2-Acetylamino-4-methyl-thiazole-5-carboxylic acid [1-(4-{3-[4-(2-methoxy-ethoxy)-phenoxy]-azetidin-1-yl}-phenyl)-ethyl]-amide

HRID 40531Notes

Reaction equation

[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:16]=[CH:15][C:9]([O:10][CH:11]2[CH2:14][NH:13][CH2:12]2)=[CH:8][CH:7]=1.Br[C:18]1[CH:23]=[CH:22][C:21]([C@@H:24]([NH:26][C:27]([C:29]2[S:33][C:32]([NH:34][C:35](=[O:37])[CH3:36])=[N:31][C:30]=2[CH3:38])=[O:28])[CH3:25])=[CH:20][CH:19]=1.CC([O-])(C)C.[Na+].O1CCOCC1>CO.O>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:16]=[CH:15][C:9]([O:10][CH:11]2[CH2:14][N:13]([C:18]3[CH:23]=[CH:22][C:21]([C@@H:24]([NH:26][C:27]([C:29]4[S:33][C:32]([NH:34][C:35](=[O:37])[CH3:36])=[N:31][C:30]=4[CH3:38])=[O:28])[CH3:25])=[CH:20][CH:19]=3)[CH2:12]2)=[CH:8][CH:7]=1

Participants

Conditions

Temperature: 45 °C

Procedure

100 mg (0.39 mmol) 3-[4-(2-Methoxy-ethoxy)-phenoxy]-azetidine (IX.4), 165 mg (0.43 mmol) (S)-2-acetylamino-4-methyl-thiazole-5-carboxylic acid [1-(4-bromo-phenyl)-ethyl]-amide (I.6), 45 mg (0.06 mmol) chloro(2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) and 150 mg (1.56 mmol) NaOtBu are combined under an argon atmosphere and 1,4-dioxane (4.0 mL) is added. The mixture is stirred for 12 h at 45° C. Some water and methanol are added and the mixture is filtered and purified by HPLC (Zorbax, acetronitrile/H2O (+0.1% TFA)) to yield the desired product.

Workup

filtrationthe mixture is filtered
custompurified by HPLC (Zorbax, acetronitrile/H2O (+0.1% TFA))

Sources & evidence

ORD record: ord-e85922c7c8244647b6cd42a4e332475c
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530461B2

Reaction notes

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