Acetic Acid → N-{3-[6-(4-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-phenylamino)4-methyl-5-oxo-4,5-dihydro-pyrazin-2-yl]-2-methyl-phenyl}4-tert-butyl-benzamide

HRID 551871Notes

Reaction equation

HRID 551871 reaction equation
[C:1]([C:5]1[CH:37]=[CH:36][C:8]([C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]3[N:19]=[C:20]([NH:26][C:27]4[CH:32]=[CH:31][C:30]([CH:33]=O)=[CH:29][CH:28]=4)[C:21](=[O:25])[N:22]([CH3:24])[CH:23]=3)[C:13]=2[CH3:35])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH:38][CH2:39][CH2:40][NH:41][CH2:42][CH2:43][OH:44].C(O)(=O)C.[BH4-].[Na+]>CO>[OH:38][CH2:39][CH2:40][N:41]([CH2:33][C:30]1[CH:31]=[CH:32][C:27]([NH:26][C:20]2[C:21](=[O:25])[N:22]([CH3:24])[CH:23]=[C:18]([C:14]3[C:13]([CH3:35])=[C:12]([NH:11][C:9](=[O:10])[C:8]4[CH:7]=[CH:6][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:37][CH:36]=4)[CH:17]=[CH:16][CH:15]=3)[N:19]=2)=[CH:28][CH:29]=1)[CH2:42][CH2:43][OH:44]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8113DiethanolamineHCID 4311764Sodium borohydrideHCID 587291394-tert-Butyl-N-{3-[6-(4-formyl-phenylamino)-4-methyl-5-oxo-4,5-dihydro-pyrazin-2-yl]-2-methyl-phenyl}-benzamide

Product 1

HCID 58729014N-{3-[6-(4-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-phenylamino)4-methyl-5-oxo-4,5-dihydro-pyrazin-2-yl]-2-methyl-phenyl}4-tert-butyl-benzamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-tert-butyl-N-{3-[6-(4-formyl-phenylamino)-4-methyl-5-oxo-4,5-dihydro-pyrazin-2-yl]-2-methyl-phenyl}-benzamide (4) (110 mg; 0.22 mmol) was dissolved in methanol (10 mL) and 1 mL 2-(2-hydroxy-ethylamino)-ethanol was added. To the stirring reaction solution was then added 0.25 mL glacial acetic acid, followed by 0.25 g powdered molecular sieves (4 Å; activated) and the resulting slurry allowed to stir at rt for 4 hr under N2, then heated to 50° C. After 3 hr at 50° C., the reaction was cooled to rt and excess NaBH4 powder (0.5 g) was added portionwise to the stirring slurry. After gas evolution ceased, the reaction slurry was then adsorbed directly onto silica gel and was chromatographed using methanol/CH2Cl2 (1:9) as eluent to provide N-{3-[6-(4-{[bis-(2-hydroxy-ethyl)-amino]-methyl}-phenylamino)-4-methyl-5-oxo-4,5-dihydro-pyrazin-2-yl]-2-methyl-phenyl}-4-tert-butyl-benzamide (5) (75 mg) as an off-white solid. MS 584.24 (M+H).

Workup

  1. customTo the stirring reaction solution
  2. temperatureheated to 50° C
  3. waitAfter 3 hr at 50° C.
  4. temperaturethe reaction was cooled to rt
  5. customwas chromatographed

Sources & evidence

ORD record
ord-905e040e3caa4816870f4f353ed85bd9
Source dataset
uspto-grants-2011_05
Patent number
US07947835B2

Reaction notes

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