4-Methylmorpholine → (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino)-4-methylpentanoic acid cyanomethylamide

HRID 1880535ノート

反応式

HRID 1880535 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:16][C@@H:17]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:18]([OH:20])=O)[C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[NH2:41][CH2:42][C:43]#[N:44].P(O)([O-])([O-])=O.[Na+].[Na+]>C1COCC1.C(OCC)(=O)C>[C:42]([CH2:43][NH:44][C:18](=[O:20])[C@@H:17]([NH:16][C@@H:8]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1)[CH2:21][CH:22]([CH3:23])[CH3:24])#[N:41]

参加物

8

反応物 5

HCID 79724-Methylmorpholine2 回HCID 24203Sodium Phosphate, DibasicHCID 62365Isobutyl chloroformateHCID 11491918Aminoacetonitrile hydrochlorideHCID 67298368HCID 67298368、化合物

生成物 1

HCID 86590549(2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino)-4-methylpentanoic acid cyanomethylamide

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentanoic acid (1.17 g, 2.86 mmol) in THF (20 mL) at −10° C. were added 4-methylmorpholine (0.315 mL, 2.86 mmol) and isobutyl chloroformate (0.371 mL, 2.86 mmol). The reaction mixture was stirred for 10 minutes, whereupon aminoacetonitrile hydrochloride (0.318 g, 3.43 mmol) was added, followed by 4-methylmorpholine (0.315 mL, 2.86 mmol). The solution was stirred for 90 minutes. Ethyl acetate (30 mL) and aqueous disodium phosphate (30 mL) were added. The organic phase was separated, washed with brine, dried over MgSO4, and evaporated to dryness. The product was purified on a short plug of silica gel (10-50% ethyl acetate/hexane gradient elution) to give (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentanoic acid cyanomethylamide.

後処理

  1. additionwas added
  2. customThe organic phase was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe product was purified on a short plug of silica gel (10-50% ethyl acetate/hexane gradient elution)

出典と根拠

ORDレコード
ord-5c625eefde8f4ab7baef2c993b58089b
出典データセット
uspto-grants-2012_11
特許番号
US08318748B2

反応ノート

読み込み中…