Pyridine → HCID 118159242, compound

HRID 713274Notes

Reaction equation

HRID 713274 reaction equation
[OH:1][C:2]([C:4](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].N1C=CC=CC=1.C(OC(=O)C)(=O)C>C(Cl)Cl>[C:2]([N:35]1[CH2:36][CH2:37][C:26]2[C:27](=[N:28][C:29]([NH:30][CH:31]([CH3:33])[CH3:32])=[C:24]([N:21]3[CH2:20][CH2:19][CH:18]([O:17][C:16]4[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][C:9]=4[F:8])[CH2:23][CH2:22]3)[N:25]=2)[CH2:34]1)(=[O:1])[CH3:4]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 131734026HCID 131734026, compound

Product 1

HCID 118159242HCID 118159242, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 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 (33.5 mg, 0.064 mmol) in DCM (639 μL) at 0° C. was added pyridine (15.5 μL, 0.192 mmol), followed by acetic anhydride (12.0 μL, 0.128 mmol). The reaction was allowed to stir for 45 min, gradually warming to room temperature. The reaction was concentrated under reduced pressure and purified directly by HPLC Method B, with the exception that a Waters SunFire™ C18, 5 nm, ID 30×75 mm column was used, using a 40% to 70% ACN gradient to give the title compound, as a TFA salt, as a yellow solid (7.1 mg, 20%). 1H NMR (400 MHz, methanol-d4, mixture of rotamers) δ ppm 1.31 (m, 6H), 2.02 (m, 2H), 2.20 (m, 5H), 2.74 (t, J=5.9 Hz, 0.7H), 2.85 (m, 1.3H), 3.14 (m, 2H), 3.43 (m, 2H), 3.83 (t, J=5.9 Hz, 1.3H), 3.87 (t, J=5.9 Hz, 0.7H), 4.14 (m, 1H), 4.60 (s, 0.7H), 4.64 (s, 1.3H), 4.80 (m, 1H), 7.34 (m, 1H), 7.54 (m, 2H); ESI-MS m/z [M+H]+ 453.5.

Workup

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

Sources & evidence

ORD record
ord-79b919bb67cc4671a2a3056d2fb8fadd
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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