2-Methoxyethylamine → 7-(6-(2-Hydroxypropan-2-yl)pyridin-3-yl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

HRID 1525503Notes

Reaction equation

HRID 1525503 reaction equation
Br[C:2]1[N:7]=[C:6]2[N:8]([CH2:13][CH2:14][O:15][CH3:16])[C:9](=[O:12])[CH2:10][NH:11][C:5]2=[N:4][CH:3]=1.Br[C:18]1[C:19]([NH:25][CH2:26][C:27](OCC)=O)=NC=C(Br)N=1.[CH3:32]OCCN.[CH:37](N(C(C)C)CC)([CH3:39])[CH3:38].C(OCC)(=O)C.[OH2:52]>CS(C)=O.C(O)(=O)C>[OH:52][C:37]([C:19]1[N:25]=[CH:26][C:27]([C:2]2[N:7]=[C:6]3[N:8]([CH2:13][CH2:14][O:15][CH3:16])[C:9](=[O:12])[CH2:10][NH:11][C:5]3=[N:4][CH:3]=2)=[CH:32][CH:18]=1)([CH3:39])[CH3:38]

Participants

8

Reactant 5

HCID 80182-MethoxyethylamineHCID 81531DiisopropylethylamineHCID 22728543Water ethylacetateHCID 57550751Ethyl 2-(3,5-dibromopyrazin-2-ylamino)acetateHCID 866446527-Bromo-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

Product 1

HCID 582983337-(6-(2-Hydroxypropan-2-yl)pyridin-3-yl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-oneYield 27%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
150 °C

Procedure

7-Bromo-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one. Ethyl 2-(3,5-dibromopyrazin-2-ylamino)acetate (See Example 1.C) (1 equiv), 2-methoxyethanamine (1 equiv), diisopropylethylamine (3 equiv), were suspended in dimethylsulfoxide and heated in an Emrys Biotage microwave reactor at 150° C. for 1 h. Standard ethyl acetate/water work up gave crude material, which was suspended in 99.7% acetic acid. The reaction was sealed, heated to 120° C. and allowed to stir for 2 h. The reaction was extracted in ethyl acetate. The organic layers were pooled and washed with saturated sodium bicarbonate, followed by brine and dried over magnesium sulfate. Concentration and flash column chromatography (0-100% ethyl acetate in hexanes) gave the desired product in 27% yield over two steps. MS (ESI) m/z 287.4 [M]+, 289.4 [M+2]+.

Workup

  1. customThe reaction was sealed
  2. temperatureheated to 120° C.
  3. extractionThe reaction was extracted in ethyl acetate
  4. washwashed with saturated sodium bicarbonate
  5. dry with materialdried over magnesium sulfate
  6. concentrationConcentration and flash column chromatography (0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-1d347098d8844827a726ab5856159f0e
Source dataset
uspto-grants-2015_07
Patent number
US09079900B2

Reaction notes

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