Triethylamine → Cyclopropyl(2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-3-(isopropylamino)-7,8-dihydropyrido[3,4-b]pyrazin-6(5H)-yl)methanone

HRID 713268Notes

Reaction equation

HRID 713268 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.[CH:44]1([C:47](Cl)=[O:48])[CH2:46][CH2:45]1>C(Cl)Cl>[CH:44]1([C:47]([N:29]2[CH2:30][CH2:31][C:20]3[C:21](=[N:22][C:23]([NH:24][CH:25]([CH3:27])[CH3:26])=[C:18]([N:15]4[CH2:14][CH2:13][CH:12]([O:11][C:10]5[CH:32]=[CH:33][C:34]([F:36])=[CH:35][C:9]=5[F:8])[CH2:17][CH2:16]4)[N:19]=3)[CH2:28]2)=[O:48])[CH2:46][CH2:45]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 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 118159281Cyclopropyl(2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-3-(isopropylamino)-7,8-dihydropyrido[3,4-b]pyrazin-6(5H)-yl)methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 (18.0 mg, 0.035 mmol) in DCM (348 μL) at room temperature was added triethylamine (14.5 μL, 0.104 mmol) and cyclopropanecarbonyl chloride (6.4 μL, 0.070 mmol). The reaction was stirred for 10 min at room temperature. The reaction mixture was concentrated under reduced pressure and was purified by HPLC Method B, with the exception that a Waters SunFire™ C18, 5 μm, ID 30×75 mm column was used, using a 50% to 90% ACN gradient to give the title compound, as a TFA salt, as a yellow film (3.3 mg, 16%). 1H NMR (400 MHz, methanol-d4, mixture of rotamers) δ ppm 0.81-0.96 (m, 4H), 1.29 (m, 7H), 1.90-2.18 (m, 4H), 2.73 (m, 0.7H), 2.87 (m, 1.3H), 3.07 (m, 2H), 3.42 (m, 2H), 3.88 (m, 0.7H), 4.06 (t, J=5.7 Hz, 1.3H), 4.14 (m, 1H), 4.49 (m, 1H), 4.62 (s, 1.3H), 4.80 (s, 0.7H), 6.88 (m, 1H), 6.99 (ddd, J=11.2, 8.5, 3.0 Hz, 1H), 7.18 ppm (td, J=9.2, 5.6 Hz, 1H); ESI-MS m/z [M+H]+ 472.5.

Workup

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

Sources & evidence

ORD record
ord-444270cf2bfe4c5dbd5f79bbe0b98401
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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