Dimethylformamide → HCID 57973796、化合物

HRID 1863920ノート

反応式

HRID 1863920 の反応式
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11](O)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.FC1N(C)CC[NH+]1C.CN(C=O)C.O.[NH2:45][NH2:46]>C(N(CC)CC)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11]([NH:45][NH2:46])=[O:12])([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 24654Hydrazine hydrate (1:1)HCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acid2 回HCID 44558572HCID 44558572、化合物

生成物 1

HCID 57973796HCID 57973796、化合物

試薬・触媒・溶媒 1

HCID 8471Triethylamine溶媒

実験手順

A dried flask was charged with 1.00 g (3 mmol) of (3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (Intermediate 3) and 865 mg (3.3 mmol) of 2-fluoro-1,3-dimethylimidazolidinium hexafluorophosphate, followed by 7.5 mL of anhydrous DMF. The resulting solution was stirred under nitrogen gas with cooling in an ice bath as 0.835 mL of triethylamine was added by syringe through a septum, and this was followed by 0.291 mL (300 mg, 6 mmol) of hydrazine hydrate. After several min, the ice bath was removed, and the mixture was allowed to warm to room temperature. After 1 h, 40 mL of water was added very gradually by syringe, accompanied by vigorous stirring. This resulted in precipitation of product. One hour later, the solid was collected on a filter, washed generously with water, and dried. The crude product was dissolved in dichloromethane-methanol and evaporated onto several grams of silica gel, which was loaded onto the top of a silica gel column. Flash chromatography (1-4% methanol in dichloromethane) provided the title compound as a white solid, mp 168-168.5° C. LC-MS 248 (M+1-Boc).

後処理

  1. additionwas added by syringe through a septum
  2. customAfter several min, the ice bath was removed
  3. addition40 mL of water was added very gradually by syringe
  4. customThis resulted in precipitation of product
  5. customOne hour later, the solid was collected on a filter
  6. washwashed generously with water
  7. customdried
  8. dissolutionThe crude product was dissolved in dichloromethane-methanol
  9. customevaporated onto several grams of silica gel, which

出典と根拠

ORDレコード
ord-d5a1850137e84a0f8ec520406a1fd9fb
出典データセット
uspto-grants-2009_12
特許番号
US07625888B2

反応ノート

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