Formaldehyde → HCID 118159319, compound

HRID 713279Notes

Reaction equation

HRID 713279 reaction equation
O[C:2](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=O.CCN(C(C)C)C(C)C.[Na]>CO>[F:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][C:16]=1[O:17][CH:18]1[CH2:19][CH2:20][N:21]([C:24]2[N:25]=[C:26]3[CH2:37][CH2:36][N:35]([CH3:2])[CH2:34][C:27]3=[N:28][C:29]=2[NH:30][CH:31]([CH3:33])[CH3:32])[CH2:22][CH2:23]1)[C:12]#[N:13]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 81531DiisopropylethylamineHCID 5360545SodiumHCID 131734026HCID 131734026, compound

Product 1

HCID 118159319HCID 118159319, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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 (12.8 mg, 0.024 mmol) and formaldehyde (2.2 mg, 0.027 mmol) in MeOH (244 μL) at room temperature was treated with DIPEA (8.5 μL, 0.049 mmol) and sodium triacetoxyhydroborate (10.3 mg, 0.049 mmol). The reaction mixture was stirred for 45 min at room temperature. The crude reaction mixture was 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 30% to 55% ACN gradient to give the title compound (about 90% purity), as a TFA salt, as a pale yellow solid. (6.0 mg, 46%). 1H NMR (400 MHz, methanol-d4) δ ppm 1.24 (d, J=6.6 Hz, 6H), 1.98 (m, 2H), 2.19 (m, 2H), 3.08 (m, 7H), 3.38 (m, 3H), 3.76 (br s, 1H), 4.16 (m, 1H), 4.29 (m, 2H), 4.79 (m, 1H), 7.34 (m, 1H), 7.53 (m, 2H); ESI-MS m/z [M+H]+ 425.5.

Workup

  1. customThe crude reaction mixture
  2. customwas purified 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-79276a55a7b742e89c4d4f8bc2ce9b5c
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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