Dimethylcarbamoyl Chloride → HCID 118159116, compound

HRID 713278Notes

Reaction equation

HRID 713278 reaction equation
OC(C(F)(F)F)=O.[F:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][C:16]=1[O:17][CH:18]1[CH2:23][CH2:22][N:21]([C:24]2[N:25]=[C:26]3[CH2:37][CH2:36][NH:35][CH2:34][C:27]3=[N:28][C:29]=2[NH:30][CH:31]([CH3:33])[CH3:32])[CH2:20][CH2:19]1)[C:12]#[N:13].C(N(CC)CC)C.[CH3:45][N:46]([CH3:50])[C:47](Cl)=[O:48]>C(Cl)Cl>[C:12]([C:11]1[CH:14]=[CH:15][C:16]([O:17][CH:18]2[CH2:19][CH2:20][N:21]([C:24]3[N:25]=[C:26]4[CH2:37][CH2:36][N:35]([C:47]([N:46]([CH3:50])[CH3:45])=[O:48])[CH2:34][C:27]4=[N:28][C:29]=3[NH:30][CH:31]([CH3:33])[CH3:32])[CH2:22][CH2:23]2)=[C:9]([F:8])[CH:10]=1)#[N:13]

Participants

5

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 1317340263-fluoro-4-((1-(3-(isopropylamino)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-yl)piperidin-4-yl)oxy)benzonitrile TFA salt

Product 1

HCID 118159116HCID 118159116, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-fluoro-4-((1-(3-(isopropylamino)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-yl)piperidin-4-yl)oxy)benzonitrile TFA salt (32.5 mg, 0.062 mmol) in DCM (620 μL) at 0° C. was treated with triethylamine (25.9 μL, 0.186 mmol) and dimethylcarbamic chloride (11.4 μL, 0.124 mmol). The reaction mixture was allowed to gradually warm to room temperature and stir for 1 h. The reaction mixture was concentrated under reduced pressure and purified directly by HPLC Method B, with the exception that a Waters SunFire™ C18, 5 μm, ID 30×75 mm column was used, using a 40% to 70% ACN gradient to give the title compound in (about 90% purity), as a TFA salt, as a yellow solid (6.8 mg, 18%). 1H NMR (400 MHz, methanol-d4) δ ppm 1.29 (m, 6H), 2.02 (m, 2H), 2.19 (m, 2H), 2.81 (t, J=5.3 Hz, 2H), 2.91 (s, 5H), 3.17 (m, 3H), 3.43 (m, 2H), 3.56 (t, J=5.6 Hz, 2H), 4.13 (m, 1H), 4.32 (s, 2H), 4.80 (m, 1H), 7.34 (m, 1H), 7.54 (t, J=10.9 Hz, 2H); ESI-MS m/z [M+H]+ 482.5.

Workup

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

Sources & evidence

ORD record
ord-2d8edb984737466f8cbe4479869f67ef
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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