Ammonium Chloride → HCID 58256475, compound

HRID 1967153Notes

Reaction equation

[C:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[S:12][C:13]([C:19]3[C:24]([F:25])=[CH:23][C:22]([C:26]([OH:29])([CH3:28])[CH3:27])=[CH:21][C:20]=3[F:30])=[CH:14][C:15]=2[C:16]([NH2:18])=[O:17])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:31][Mg]Cl.[NH4+].[Cl-]>C1COCC1>[F:25][C:24]1[CH:23]=[C:22]([C:26]([OH:29])([CH3:27])[CH3:28])[CH:21]=[C:20]([F:30])[C:19]=1[C:13]1[S:12][C:11]([NH:10][C:7]2[CH:6]=[CH:5][C:4]([C:1]([OH:3])([CH3:31])[CH3:2])=[CH:9][CH:8]=2)=[C:15]([C:16]([NH2:18])=[O:17])[CH:14]=1

Participants

Conditions

Temperature: 0 °C

Procedure

2-[(4-acetylphenyl)amino]-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide (50 mg, 0.116 mmol) was taken up in THF (1 mL) and cooled to 0° C. Methylmagnesium chloride (0.136 mL, 0.407 mmol) was added and stirring continued at 0° C. for 2.5 hours. After this time, additional THF (1 mL) was added to aid solubility, the mixture was allowed to warm to room temperature and stirring continued for 2.5 hours. Saturated NH4Cl was added and the products extracted into EtOAc (×2). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by MPLC (0-10% MeOH—CHCl3) followed by MPLC (12-100% EtAOc-hexanes) gave 5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-{[4-(1-hydroxy-1-methylethyl)phenyl]amino}thiophene-3-carboxamide as a brown solid.

Workup

temperatureto warm to room temperature
stirringstirring
waitcontinued for 2.5 hours
extractionthe products extracted into EtOAc (×2)
washThe combined organic extracts were washed with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customPurification of the residue by MPLC (0-10% MeOH—CHCl3)

Sources & evidence

ORD record: ord-4a0635bd1c2e44528b5d0eafb3096989
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08420695B2

Reaction notes

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