Ethanolamine → N-Cyclopropyl-3-[3-({1-[2-({(2R)-2-hydroxy-3-[(2-hydroxyethyl)amino]propyl}oxy)phenyl]cyclopropyl}amino)-2-oxopyrazin-1(2H)-yl]-4-methylbenzamide

HRID 2070803Notes

Reaction equation

HRID 2070803 reaction equation
[CH2:1]([CH2:3][NH2:4])[OH:2].[CH:5]1([NH:8][C:9](=[O:39])[C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[C:12]([N:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=5[O:33][CH2:34][C@H:35]5[CH2:37][O:36]5)[CH2:26][CH2:25]4)[C:18]3=[O:38])[CH:11]=2)[CH2:7][CH2:6]1>CN(C=O)C>[CH:5]1([NH:8][C:9](=[O:39])[C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[C:12]([N:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=5[O:33][CH2:34][C@H:35]([OH:36])[CH2:37][NH:4][CH2:3][CH2:1][OH:2])[CH2:25][CH2:26]4)[C:18]3=[O:38])[CH:11]=2)[CH2:6][CH2:7]1

Participants

4

Reactant 2

HCID 700EthanolamineHCID 86663253(R)-N-cyclopropyl-4-methyl-3-(3-(1-(2-(oxiran-2-ylmethoxy)phenyl)cyclopropylamino)-2-oxopyrazin-1(2H)-yl)benzamide

Product 1

HCID 66686018N-Cyclopropyl-3-[3-({1-[2-({(2R)-2-hydroxy-3-[(2-hydroxyethyl)amino]propyl}oxy)phenyl]cyclopropyl}amino)-2-oxopyrazin-1(2H)-yl]-4-methylbenzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Ethanolamine (1 mL) was added to N-cyclopropyl-4-methyl-3-{3-[(1-{2-[(2R)-oxiran-2-ylmethoxy]phenyl}cyclopropyl)amino]-2-oxopyrazin-1(2H)-yl}benzamide (Example 299a, 7.81 g) in DMF (3 mL). The reaction was heated at 50° C. overnight. The reaction mixture was partitioned between water and DCM. The combined organics were dried (MgSO4), filtered and evaporated. Purification by preparative HPLC (Xbridge column, eluting with a gradient of acetonitrile in 0.2% (v/v) aqueous ammonia) gave the title product (0.102 g) after solvent removal and trituration with diethyl ether.

Workup

  1. customThe reaction mixture was partitioned between water and DCM
  2. dry with materialThe combined organics were dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customPurification by preparative HPLC (Xbridge column
  6. washeluting with a gradient of acetonitrile in 0.2% (v/v) aqueous ammonia)

Sources & evidence

ORD record
ord-91a5f3e664a5463b801f3e971ecaebea
Source dataset
uspto-grants-2012_10
Patent number
US08299246B2

Reaction notes

Loading…