Dimethylformamide → tert-Butyl 4-(1-(3-(((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-2-methyl-1H-indol-1-yl)ethyl)piperidine-1-carboxylate

HRID 2206529Notes

Reaction equation

HRID 2206529 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([N:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]([C:25](O)=[O:26])=[C:17]2[CH3:28])[CH3:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:30][CH2:31][C:32]1[C:33](=[O:41])[NH:34][C:35]([CH3:40])=[CH:36][C:37]=1[O:38][CH3:39].CN(C=O)C.CCN(C(C)C)C(C)C.CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F>O>[CH3:39][O:38][C:37]1[CH:36]=[C:35]([CH3:40])[NH:34][C:33](=[O:41])[C:32]=1[CH2:31][NH:30][C:25]([C:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:16]([CH:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:13][CH2:12]2)[CH3:15])[C:17]=1[CH3:28])=[O:26]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 89740341HCID 89740341, compoundHCID 1177807191H-Indole-3-carboxylic acid, 1-[1-[1-[(1,1-dimethylethoxy)carbonyl]-4-piperidinyl]ethyl]-2-methyl-

Product 1

HCID 117807734tert-Butyl 4-(1-(3-(((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-2-methyl-1H-indol-1-yl)ethyl)piperidine-1-carboxylateYield 65.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A 250 mL round bottom flask was charged with a magnetic stir bar, (R or S)-1-(1-(1-(tert-butoxycarbonyl)piperidin-4-yl)ethyl)-2-methyl-1H-indole-3-carboxylic acid (1.950 g, 5.05 mmol), 3-(aminomethyl)-4-methoxy-6-methylpyridin-2(1H)-one hydrochloride (2.065 g, 10.09 mmol), DMF (25.2 ml, 5.05 mmol), Hunig's base (3.52 ml, 20.18 mmol). The reaction mixture was cooled to 0° C. and COMU (2.16 g, 5.05 mmol) was added. The reaction was allowed to stir overnight to room temperature. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic extract was washed with brine, dried with MgSO4, filtered and conc., in vacuo to afford the crude material which was purified via silica gel chromatography (120 g) using MeOH/ethyl acetate (1:5) as eluent to afford the title compound (1.86 g, 3.29 mmol, 65.3% yield). LCMS 537 (M+1)+ 1H NMR (400 MHz, DMSO-d6) δ=11.83-11.71 (m, 1H), 7.80 (br. s., 1H1), 7.73 (d, J=7.6 Hz, 1H), 7.62 (d, J=7.8 Hz, 1H), 7.06 (td, J=7.1, 14.4 Hz, 2H), 6.21 (s, 1H), 4.32 (br. s., 2H), 4.16 (br. s., 1H), 4.02 (br. s., 1H), 3.85 (s, 3H), 3.75 (br. s., 1H), 2.70 (br. s., 1H), 2.58 (s, 3H), 2.37 (br. s., 1H), 2.21 (s, 3H), 1.90 (d, J=12.9 Hz, 1H), 1.53 (d, J=6.9 Hz, 3H), 1.35 (s, 10H), 1.21 (br. s., 1H), 0.89 (d, J=8.7 Hz, 1H), 0.67 (d, J=11.8 Hz, 1H).

Workup

  1. additionA 250 mL round bottom flask was charged with a magnetic stir bar
  2. extractionextracted with EtOAc
  3. extractionThe combined organic extract
  4. washwas washed with brine
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. customconc., in vacuo to afford the crude material which
  8. customwas purified via silica gel chromatography (120 g)

Sources & evidence

ORD record
ord-3e78289d1b0541e69d93ecfe9082a68a
Source dataset
uspto-grants-2016_06
Patent number
US09371331B2

Reaction notes

Loading…