Triethylamine → N-[(R)-2-[3-butoxy-3-(2-fluoro-phenyl)azetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamide

HRID 540409ノート

反応式

HRID 540409 の反応式
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.Cl.[CH2:31]([C:38]([OH:40])=O)[CH2:32][C:33]1[N:37]=[CH:36][NH:35][CH:34]=1.FC(F)(F)C(O)=O.[NH2:48][C@H:49]([CH2:68][C:69]1[CH:74]=[CH:73][C:72]([O:75][CH3:76])=[CH:71][CH:70]=1)[C:50]([N:52]1[CH2:55][C:54]([O:63][CH2:64][CH2:65][CH2:66][CH3:67])([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=2[F:62])[CH2:53]1)=[O:51]>CN(C)C=O>[CH2:64]([O:63][C:54]1([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=2[F:62])[CH2:53][N:52]([C:50](=[O:51])[C@H:49]([NH:48][C:38](=[O:40])[CH2:31][CH2:32][C:33]2[N:37]=[CH:36][NH:35][CH:34]=2)[CH2:68][C:69]2[CH:74]=[CH:73][C:72]([O:75][CH3:76])=[CH:71][CH:70]=2)[CH2:55]1)[CH2:65][CH2:66][CH3:67]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66988186(R)-2-amino-1-[3-butoxy-3-(2-fluorophenyl)azetidin-1-yl]-3-(4-methoxy-phenyl)propan-1-one trifluoroacetateHCID 178479756HCID 178479756、化合物

生成物 1

HCID 178450018N-[(R)-2-[3-butoxy-3-(2-fluoro-phenyl)azetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamide収率 57%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

81 mg (0.3 mmol) of TBTU and 0.1 ml (0.6 mmol) of triethylamine are added to a solution of 42 mg (0.25 mmol) of desamino-histidine hydrochloride in 1 ml of dimethylformamide. After stirring for 10 minutes, 119 mg (0.2 mmol) of (R)-2-amino-1-[3-butoxy-3-(2-fluorophenyl)azetidin-1-yl]-3-(4-methoxyphenyl)propan-1-one trifluoroacetate are added and the reaction medium is stirred for 64 h at ambient temperature. After extraction with a 1/2 heptane/ethyl acetate mixture, the organic phase is washed with 1N aqueous solution of sodium hydroxide and a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and evaporated. The crude product is purified by silica gel chromatography, elution being carried out with a 90/10 dichloromethane/methanol mixture. 59 mg of N—[(R)-2-[3-butoxy-3-(2-fluoro-phenyl)azetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamide are obtained in the form of a white solid with a yield of 57%.

後処理

  1. stirringthe reaction medium is stirred for 64 h at ambient temperature
  2. extractionAfter extraction with a 1/2 heptane/ethyl acetate mixture
  3. washthe organic phase is washed with 1N aqueous solution of sodium hydroxide
  4. dry with materiala saturated aqueous solution of sodium chloride, dried over magnesium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product is purified by silica gel chromatography, elution

出典と根拠

ORDレコード
ord-b68e1ff8622b4026b2265dc91f45e35d
出典データセット
uspto-grants-2014_10
特許番号
US08871187B2

反応ノート

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