1-Hydroxybenzotriazole → (2E)-3-[5-({(3R)-1-[2-(dimethylamino)benzyl]-3-pyrrolidinyl}amino)-2-pyrazinyl]-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide

HRID 2354090Notes

Reaction equation

HRID 2354090 reaction equation
[CH3:1][N:2]([CH3:27])[C:3]1[CH:26]=[CH:25][CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[CH2:10][CH2:9][C@@H:8]([NH:11][C:12]2[N:13]=[CH:14][C:15](/[CH:18]=[CH:19]/[C:20](O)=[O:21])=[N:16][CH:17]=2)[CH2:7]1.[O:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH:29]1[O:34][NH2:35].C1C=CC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:27][N:2]([CH3:1])[C:3]1[CH:26]=[CH:25][CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[CH2:10][CH2:9][C@@H:8]([NH:11][C:12]2[N:13]=[CH:14][C:15](/[CH:18]=[CH:19]/[C:20]([NH:35][O:34][CH:29]3[CH2:30][CH2:31][CH2:32][CH2:33][O:28]3)=[O:21])=[N:16][CH:17]=2)[CH2:7]1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 67128945(2E)-3-[5-({(3R)-1-[2-(dimethylamino) benzyl]-3-pyrrolidinyl}amino)-2-pyrazinyl]acrylic acid

Product 1

HCID 86628129(2E)-3-[5-({(3R)-1-[2-(dimethylamino)benzyl]-3-pyrrolidinyl}amino)-2-pyrazinyl]-N-(tetrahydro-2H-pyran-2-yloxy)acrylamideYield 49.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of crude (2E)-3-[5-({(3R)-1-[2-(dimethylamino) benzyl]-3-pyrrolidinyl}amino)-2-pyrazinyl]acrylic acid (311 mg), O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (108 mg), and HOBT (125 mg) in DMF (2.4 mL) was added WSCD (164 uL), which was stirred at room temperature for 17 hours. To the resultant was added saturated NaHCO3 aq. The mixture was extracted with AcOEt. The organic phase was washed with brine, dried over Na2SO4, filtered, and evaporated in vacuo. The residue was purified by column chromatography on silica gel to give (2E)-3-[5-({(3R)-1-[2-(dimethylamino)benzyl]-3-pyrrolidinyl}amino)-2-pyrazinyl]-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide (195 mg) as a yellow amorphous.

Workup

  1. additionwas added WSCD (164 uL), which
  2. extractionwas extracted with AcOEt
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-a6a98da1722d4d7c83a472a789ad68b1
Source dataset
uspto-grants-2010_07
Patent number
US07750155B2

Reaction notes

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