Hydroxylamine → (2E)-3-(5-{[(3R)-1-cyclohexyl-3-piperidinyl]amino}-2-pyrazinyl)-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide

HRID 226364Notes

Reaction equation

HRID 226364 reaction equation
[CH:1]1([N:7]2[CH2:12][CH2:11][CH2:10][C@@H:9]([NH:13][C:14]3[N:15]=[CH:16][C:17](/[CH:20]=[CH:21]/[C:22]([OH:24])=O)=[N:18][CH:19]=3)[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][OH:26].C1C=[CH:29][C:30]2N(O)N=N[C:31]=2[CH:32]=1.CCN=C=NCCCN(C)C.CN([CH:51]=[O:52])C>>[CH:1]1([N:7]2[CH2:12][CH2:11][CH2:10][C@@H:9]([NH:13][C:14]3[N:15]=[CH:16][C:17](/[CH:20]=[CH:21]/[C:22]([NH:25][O:26][CH:29]4[CH2:30][CH2:31][CH2:32][CH2:51][O:52]4)=[O:24])=[N:18][CH:19]=3)[CH2:8]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 5

HCID 787HydroxylamineHCID 6228DimethylformamideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 68964465(2E)-3-(5-{[(3R)-1-cyclohexyl-3-piperidinyl]amino}-2-pyrazinyl)acrylic acid

Product 1

HCID 86603671(2E)-3-(5-{[(3R)-1-cyclohexyl-3-piperidinyl]amino}-2-pyrazinyl)-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide

Conditions

Temperature
0 °C

Procedure

A mixture of (2E)-3-(5-{[(3R)-1-cyclohexyl-3-piperidinyl]amino}-2-pyrazinyl)acrylic acid (209 mg), 0-(tetrahydro-2H-pyran-2-yl)-mL) hydroxylamine (89 mg), HOBt (111 mg) and EDCI (158 mg) in DMF (4.5 mL) was stirred at 0° C. for 1 hr and the mixture was stirred at ambient temperature for 18 hrs. The reaction mixture was evaporated in vacuo and the residue was partitioned between saturated sodium bicarbonate solution and EtOAc. The organic layer was separated, washed water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (chloroform-MeOH=95-5) to give (2E)-3-(5-{[(3R)-1-cyclohexyl-3-piperidinyl]amino}-2-pyrazinyl)-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide (198 mg) as an amorphous powder.

Workup

  1. stirringthe mixture was stirred at ambient temperature for 18 hrs
  2. customThe reaction mixture was evaporated in vacuo
  3. customthe residue was partitioned between saturated sodium bicarbonate solution and EtOAc
  4. customThe organic layer was separated
  5. washwashed water and brine
  6. dry with materialdried over magnesium sulfate
  7. customevaporated in vacuo
  8. customThe residue was purified by silica gel column chromatography (chloroform-MeOH=95-5)

Sources & evidence

ORD record
ord-f0b6077abf6940c38bd384aaf77bde58
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

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