Trifluoroacetic acid → tert-Butyl (3R)-3-[({7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-5-methylhexanoate

HRID 1486334ノート

反応式

HRID 1486334 の反応式
[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15](O)=[O:16])=[C:10]2[CH:9]=[C:8]([CH3:19])[CH:7]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1.[NH2:54][C@H:55]([CH2:64][CH:65]([CH3:67])[CH3:66])[CH2:56][C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58].C(O)(C(F)(F)F)=O>CN(C=O)C.O>[F:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:2]([F:1])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15]([NH:54][C@H:55]([CH2:64][CH:65]([CH3:67])[CH3:66])[CH2:56][C:57]([O:59][C:60]([CH3:61])([CH3:62])[CH3:63])=[O:58])=[O:16])=[C:10]2[CH:9]=[C:8]([CH3:19])[CH:7]=1

参加物

8

反応物 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 2733825tert-Butyl (3R)-3-amino-5-methyl-hexanoateHCID 117859510HCID 117859510、化合物

生成物 1

HCID 117859497tert-Butyl (3R)-3-[({7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-5-methylhexanoate収率 56.9%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 100 mg (0.30 mmol, 1.0 eq.) of 7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid from Example 4A, 116 mg of TBTU (0.36 mmol, 1.2 eq.) and 0.132 ml (1.2 mmol, 4.0 eq.) of 4-methylmorpholine in 2.2 ml of DMF was admixed with 121 mg (0.60 mmol, 2.0 eq.) of tert-butyl (3R)-3-amino-5-methylhexanoate, and the mixture was stirred at RT overnight. The reaction mixture was admixed with water and TFA and purified by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.1% TFA). The product fractions were combined and concentrated. Subsequently, the residue was taken up in dichloromethane and a little methanol, and washed twice with saturated aqueous sodium hydrogencarbonate solution. The aqueous phase was extracted twice with dichloromethane. The combined organic phases were dried over sodium sulphate, filtered, concentrated and lyophilized. 88 mg of the target compound were obtained (57% of theory).

後処理

  1. custompurified by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.1% TFA)
  2. concentrationconcentrated
  3. washa little methanol, and washed twice with saturated aqueous sodium hydrogencarbonate solution
  4. extractionThe aqueous phase was extracted twice with dichloromethane
  5. dry with materialThe combined organic phases were dried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-69d050a9ca68412c98abc5486ceb8288
出典データセット
uspto-grants-2016_08
特許番号
US09422285B2

反応ノート

読み込み中…