1,2-Dichloroethane → Tert-butyl 4-(5-chloro-3-(((2,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)carbamoyl)-2-methylphenoxy)piperidine-1-carboxylate

HRID 1050465Notes

Reaction equation

HRID 1050465 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:16]([CH3:25])=[C:17]([CH:21]=[C:22]([Cl:24])[CH:23]=2)[C:18]([OH:20])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:27][CH2:28][C:29]1[C:34](=[O:35])[CH:33]=[C:32]([CH3:36])[NH:31][C:30]=1[CH3:37].ON1C2N=CC=CC=2N=N1.C(Cl)CCl.CN1CCOCC1>CN(C)C=O>[Cl:24][C:22]1[CH:21]=[C:17]([C:18](=[O:20])[NH:27][CH2:28][C:29]2[C:34](=[O:35])[CH:33]=[C:32]([CH3:36])[NH:31][C:30]=2[CH3:37])[C:16]([CH3:25])=[C:15]([CH:23]=1)[O:14][CH:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 902730033-((1-(Tert-butoxycarbonyl)piperidin-4-yl)oxy)-5-chloro-2-methylbenzoic acidHCID 902732273-(aminomethyl)-2,6-dimethylpyridin-4(1H)-one hydrochloride

Product 1

HCID 76902143Tert-butyl 4-(5-chloro-3-(((2,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)carbamoyl)-2-methylphenoxy)piperidine-1-carboxylateYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-((1-(tert-butoxycarbonyl)piperidin-4-yl)oxy)-5-chloro-2-methylbenzoic acid (140 mg, 0.379 mmol), 3-(aminomethyl)-2,6-dimethylpyridin-4(1H)-one, hydrochloride (71.4 mg, 0.379 mmol), 1-hydroxy-7-azabenzotriazole (HOAT) (77 mg, 0.568 mmol), EDC (109 mg, 0.568 mmol) and N-methylmorpholine (166 μl, 1.514 mmol) was stirred for 18 h at RT in N,N-Dimethylformamide (DMF) (3619 μl) under nitrogen. Upon completion, the reaction was poured into stirring ice-water. White solid precipitated out of solution, which was filtered and dried under high vacuum to give tert-butyl 4-(5-chloro-3-(((2,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)carbamoyl)-2-methylphenoxy)piperidine-1-carboxylate (0.095 g, 0.189 mmol, 50% yield). 1H NMR (400 MHz, DMSO-d6) δ 1.41 (s, 9 H) 1.50-1.60 (m, 2 H) 1.79-1.90 (m, 2 H) 2.06 (s, 3 H) 2.16 (s, 3 H) 2.31 (s, 3 H) 3.20-3.31 (m, 2 H) 3.49-3.63 (m, 2 H) 4.19 (d, J=4.80 Hz, 2 H) 4.59-4.78 (m, 1 H) 5.87 (s, 1 H) 6.81 (d, J=2.02 Hz, 1 H) 7.15 (d, J=1.77 Hz, 1 H) 8.22 (t, J=5.05 Hz, 1 H) 11.01 (br. s., 1 H). MS(ES) [M+H]+ 504.4.

Workup

  1. additionUpon completion, the reaction was poured
  2. customWhite solid precipitated out of solution, which
  3. filtrationwas filtered
  4. customdried under high vacuum

Sources & evidence

ORD record
ord-367810f3d8954ac2a6d23ab1ba7a28ba
Source dataset
uspto-grants-2016_07
Patent number
US09382234B2

Reaction notes

Loading…