1,2-Dichloroethane → 1-9H-fluoren-9-ylmethyl (2R,3S)-4-(3,5-difluorophenyl)-2-hydroxy-3-{[5-oxo-5-(1-piperidinyl)pentanoyl]amino}butyl(3-iodobenzyl)carbamate

HRID 14015

反応式

HRID 14015 の反応式
C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.NC(C1C=[C:20]([CH:24]=[C:25]([C:27]([N:29]([CH2:33][CH2:34][CH3:35])[CH2:30][CH2:31]C)=[O:28])C=1)[C:21]([OH:23])=O)=O.Cl.[NH2:37][C@@H:38]([CH2:68][C:69]1[CH:74]=[C:73]([F:75])[CH:72]=[C:71]([F:76])[CH:70]=1)[C@H:39]([OH:67])[CH2:40][N:41]([CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[C:62]([I:66])[CH:61]=1)[C:42](=[O:58])[O:43][CH2:44][CH:45]1[C:57]2[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=2[C:51]2[C:46]1=[CH:47][CH:48]=[CH:49][CH:50]=2.CN1CCOCC1>CN(C=O)C>[F:76][C:71]1[CH:70]=[C:69]([CH2:68][C@H:38]([NH:37][C:21](=[O:23])[CH2:20][CH2:24][CH2:25][C:27](=[O:28])[N:29]2[CH2:30][CH2:31][CH2:35][CH2:34][CH2:33]2)[C@H:39]([OH:67])[CH2:40][N:41]([CH2:59][C:60]2[CH:65]=[CH:64][CH:63]=[C:62]([I:66])[CH:61]=2)[C:42](=[O:58])[O:43][CH2:44][CH:45]2[C:46]3[CH:47]=[CH:48][CH:49]=[CH:50][C:51]=3[C:52]3[C:57]2=[CH:56][CH:55]=[CH:54][CH:53]=3)[CH:74]=[C:73]([F:75])[CH:72]=1

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 223948913-Carbamoyl-5-dipropylcarbamoyl-benzoic acidHCID 865858561-9H-fluoren-9-ylmethyl(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl(3-iodobenzyl)carbamate hydrochloride

生成物 1

HCID 587598521-9H-fluoren-9-ylmethyl (2R,3S)-4-(3,5-difluorophenyl)-2-hydroxy-3-{[5-oxo-5-(1-piperidinyl)pentanoyl]amino}butyl(3-iodobenzyl)carbamate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

HOBt (81 mg, 0.6 mmole) and EDC (105 mg, 0.55 mmole) are added to 1-carboxy-5-piperdinylglutaramide (IX, 100 mg, 0.5 mmole) in DMF (2 ml). The acid is activated 60 minutes then treated with 1-9H-fluoren-9-ylmethyl(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl(3-iodobenzyl)carbamate hydrochloride (XXXV, EXAMPLE 590, 300 mg, 0.43 mmole) and NMM (0.19 ml, 1.72 mmole). The reaction is stirred 3 hours then concentrated under reduced pressure. The residue is partitioned between ethyl acetate and saturated aqueous bicarbonate. The organic phases are washed with aqueous potassium bisulfate, saline, dried over sodium sulfate and finally concentrated under reduced pressure to give crude product. Purification via flash chromatography with ethyl acetate/hexane (50/50) then methanol/ethyl acetate (10/90) gives the title compound, M+H=838.

後処理

  1. concentrationthen concentrated under reduced pressure
  2. customThe residue is partitioned between ethyl acetate and saturated aqueous bicarbonate
  3. washThe organic phases are washed with aqueous potassium bisulfate, saline
  4. dry with materialdried over sodium sulfate
  5. concentrationfinally concentrated under reduced pressure
  6. customto give crude product
  7. customPurification via flash chromatography with ethyl acetate/hexane (50/50)

出典と根拠

ORDレコード
ord-b472e8f157bb4c5391c51d7ec4a7babc
出典データセット
uspto-grants-2010_06
特許番号
US07727997B2

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