1,2-Dichloroethane → (S)-tert-butyl (1-(4-(3-carbamoylpyridin-4-yl)-3-fluorophenoxy)-4-methylpentan-2-yl)carbamate

HRID 1398285Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:23]([C:24](O)=[O:25])=[CH:22][N:21]=[CH:20][CH:19]=2)=[C:14]([F:27])[CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=[N:42]C=2C=1.[Cl-].[NH4+].C(N(C(C)C)CC)(C)C>CN(C=O)C>[C:24]([C:23]1[CH:22]=[N:21][CH:20]=[CH:19][C:18]=1[C:15]1[CH:16]=[CH:17][C:12]([O:11][CH2:10][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])[CH2:28][CH:29]([CH3:31])[CH3:30])=[CH:13][C:14]=1[F:27])(=[O:25])[NH2:42]

Participants

Conditions

Temperature: 0 °C

Procedure

(S)-4-(4-((2-((tert-butoxycarbonyl)amino)-4-methylpentyl)oxy)-2-fluorophenyl)nicotinic acid (75 mg, 0.173 mmol) was taken in DMF (2 mL) and cooled to 0° C. To the solution was added EDC (49.9 mg, 0.260 mmol) and HOBT (53.1 mg, 0.347 mmol). After stirring the reaction mixture for 5 min, ammonium chloride (55.7 mg, 1.040 mmol) was added and the resultant mixture was stirred for 5 min. Diisopropylethylamine (0.121 mL, 0.694 mmol) was added and the mixture was allowed to stir at room temperature for an additional 12 h. The mixture was then quenched with ice and the residue was filtered and dried under vacuum to afford (S)-tert-butyl (1-(4-(3-carbamoylpyridin-4-yl)-3-fluorophenoxy)-4-methylpentan-2-yl)carbamate (50 mg, 0.098 mmol, 57% yield) as a light yellow solid. LC/MS (ESI) m/e 432.2 [(M+H)+, calcd for C23H31FN3O4 432.2]; LC/MS retention time (method C): tR=1.83 min.

Workup

stirringto stir at room temperature for an additional 12 h
customThe mixture was then quenched with ice
filtrationthe residue was filtered
customdried under vacuum

Sources & evidence

ORD record: ord-194ecb7e756349aabbdadd18096d53aa
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901305B2

Reaction notes

Loading…