Triethylamine → N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(pyrimidin-2-yl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide

HRID 1527020Notes

Reaction equation

HRID 1527020 reaction equation
Cl[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.Cl.[CH3:9][O:10][C:11]1[CH:16]=[C:15]([CH3:17])[NH:14][C:13](=[O:18])[C:12]=1[CH2:19][NH:20][C:21]([C:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]([CH:32]([CH:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)[CH3:33])[C:24]=1[CH3:40])=[O:22].CCN(CC)CC>CCO>[CH3:9][O:10][C:11]1[CH:16]=[C:15]([CH3:17])[NH:14][C:13](=[O:18])[C:12]=1[CH2:19][NH:20][C:21]([C:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]([CH:32]([CH:34]2[CH2:35][CH2:36][N:37]([C:2]3[N:7]=[CH:6][CH:5]=[CH:4][N:3]=3)[CH2:38][CH2:39]2)[CH3:33])[C:24]=1[CH3:40])=[O:22]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 744042-ChloropyrimidineHCID 117780708HCID 117780708, compound2×

Product 1

HCID 117780899N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(pyrimidin-2-yl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamideYield 64.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a re-sealable vial was added 2-chloropyrimidine (185 mg, 1.611 mmol), (R or S)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(piperidin-4-yl)ethyl)-1H-indole-3-carboxamide hydrochloride (508 mg, 1.074 mmol) (Compound 326), and EtOH (8 mL). To this solution was added Et3N (449 μl, 3.22 mmol). The vial was sealed and heated to 100° C. overnight. The solution was allowed to cool to room temperature and concentrated in vacuo. The crude residue was purified via silica gel chromatography (hexanes: (3:2 DCM:IPA)) to afford the title compound as a solid (357 mg, 0.694 mmol, 64.6% yield). LCMS 515 (M+1)+; 1H NMR (DMSO-d6, 400 MHz) δ 11.60 (s, 1 H), 8.30 (d, J=4.7 Hz, 2 H), 7.76 (d, J=7.6 Hz, 1 H), 7.73-7.64 (m, 2 H), 7.14-7.01 (m, 2 H), 6.55 (t, J=4.7 Hz, 1 H), 6.15 (s, 1 H), 4.84-4.75 (m, 1 H), 4.57-4.47 (m, 1 H), 4.33 (d, J=4.2 Hz, 2 H), 4.22-4.11 (m, 1 H), 3.84 (s, 3 H), 2.92-2.81 (m, 1 H), 2.63-2.52 (m, 4 H), 2.20 (s, 3H), 2.05-1.94 (m, 1 H), 1.61-1.49 (m, 4 H), 1.34-1.21 (m, 1 H), 1.04-0.91 (m, 1 H), 0.83-0.75 (m, 1 H).

Workup

  1. customThe vial was sealed
  2. temperatureto cool to room temperature
  3. concentrationconcentrated in vacuo
  4. customThe crude residue was purified via silica gel chromatography (hexanes: (3:2 DCM:IPA))

Sources & evidence

ORD record
ord-141dbe541e7d4ef18144d7923e64810c
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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