Triethylamine → 2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-3-(isopropylamino)-N-(2-methoxyethyl)-7,8-dihydropyrido[3,4-b]pyrazine-6(5H)-carboxamide

HRID 713271Notes

Reaction equation

HRID 713271 reaction equation
OC(C(F)(F)F)=O.[F:8][C:9]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:10]=1[O:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]2[N:19]=[C:20]3[CH2:31][CH2:30][NH:29][CH2:28][C:21]3=[N:22][C:23]=2[NH:24][CH:25]([CH3:27])[CH3:26])[CH2:14][CH2:13]1.C(N(CC)CC)C.[N:44]([CH2:47][CH2:48][O:49][CH3:50])=[C:45]=[O:46]>C(Cl)Cl>[F:8][C:9]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:10]=1[O:11][CH:12]1[CH2:13][CH2:14][N:15]([C:18]2[N:19]=[C:20]3[CH2:31][CH2:30][N:29]([C:45]([NH:44][CH2:47][CH2:48][O:49][CH3:50])=[O:46])[CH2:28][C:21]3=[N:22][C:23]=2[NH:24][CH:25]([CH3:27])[CH3:26])[CH2:16][CH2:17]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 144050071-Isocyanato-2-methoxyethaneHCID 1317340252-(4-(2,4-difluorophenoxy)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt

Product 1

HCID 1181593342-(4-(2,4-difluorophenoxy)piperidin-1-yl)-3-(isopropylamino)-N-(2-methoxyethyl)-7,8-dihydropyrido[3,4-b]pyrazine-6(5H)-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt (39.0 mg, 0.075 mmol) in DCM (754 μL) at 0° C. was added triethylamine (31.5 μL, 0.226 mmol) and 1-isocyanato-2-methoxyethane (11.8 μL, 0.113 mmol). The reaction mixture was stirred for 1 h at 0° C. The reaction mixture was concentrated under reduced pressure and purified by HPLC Method B, with the exception that a Waters SunFire™ C18, 5 μm, ID 30×75 mm column was used, using a 45% to 70% ACN gradient to give the title compound, as a TFA salt, as a yellow oil (24.5 mg, 52.6%). 1H NMR (400 MHz, methanol-d4) δ ppm 1.32 (d, J=6.6 Hz, 6H), 1.97 (m, 2H), 2.14 (m, 2H), 2.77 (t, J=5.8 Hz, 2H), 3.12 (m, 2H), 3.37 (m, 5H), 3.46 (m, 4H), 3.71 (t, J=5.8 Hz, 2H), 4.13 (m, 1H), 4.50 (m, 3H), 6.88 (m, 1H), 6.98 (ddd, J=11.2, 8.5, 3.0 Hz, 1H), 7.17 (td, J=9.2, 5.6 Hz, 1H); ESI-MS m/z [M+H]+ 505.6.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. custompurified by HPLC Method B, with the exception that a Waters SunFire™ C18, 5 μm, ID 30×75 mm column

Sources & evidence

ORD record
ord-7f354ffe8bc5482d94dff30632fe5f3c
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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