Dimethylcarbamoyl Chloride → Trifluoroacetic acid

HRID 713294Notes

Reaction equation

HRID 713294 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[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:29]=[C:28]3[CH2:30][NH:31][CH2:32][CH2:33][C:27]3=[N:26][C:25]=2[NH:34][CH:35]([CH3:37])[CH3:36])[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:29]=[C:28]4[CH2:30][N:31]([C:47]([N:46]([CH3:50])[CH3:45])=[O:48])[CH2:32][CH2:33][C:27]4=[N:26][C:25]=3[NH:34][CH:35]([CH3:37])[CH3:36])[CH2:22][CH2:23]2)=[C:9]([F:8])[CH:10]=1)#[N:13].[C:2]([OH:3])([C:4]([F:7])([F:6])[F:5])=[O:1]

Participants

6

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 118159356HCID 118159356, compound

Product 2

HCID 6422Trifluoroacetic acidYield 260.9%HCID 118159223HCID 118159223, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-fluoro-4-((1-(2-(isopropylamino)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-yl)piperidin-4-yl)oxy)benzonitrile TFA salt (20.7 mg, 0.039 mmol) and triethylamine (0.017 mL, 0.118 mmol) in DCM (0.5 mL) was added dimethylcarbamoyl chloride (7.3 μL, 0.079 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min and then concentrated via rotary evaporation. The crude material was diluted with DMSO, filtered, rinsed with DMSO, and purified by HPLC Method B, with the exception that a Waters XSelect® CSH C18, 5 μm, ID 4.6×50 mm was used, using a 30% to 70% ACN gradient to give the title compound as a TFA salt (11.6 mg, 49.4%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.13-1.26 (m, 6H), 1.87-1.96 (m, 2H), 2.08-2.16 (m, 2H), 2.81-2.99 (m, 6H), 3.25-3.42 (m, 3H), 3.65-3.71 (m, 1H), 4.12-4.19 (m, 2H), 4.25-4.31 (m, 1H), 4.82-4.88 (m, 1H), 5.89 (d, J=8.3 Hz, 1H), 7.50 (t, J=8.6 Hz, 1H), 7.66-7.71 (m, 1H), 7.87 (dd, J=11.4, 2.0 Hz, 1H), 9.96 (br s, 1H); ESI-MS m/z [M+H]+ 482.5.

Workup

  1. concentrationconcentrated via rotary evaporation
  2. additionThe crude material was diluted with DMSO
  3. filtrationfiltered
  4. washrinsed with DMSO
  5. custompurified by HPLC Method B, with the exception that a Waters XSelect® CSH C18, 5 μm, ID 4.6×50 mm

Sources & evidence

ORD record
ord-feb9a01bd0dd4b5388fd02530e71cef0
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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