Diisopropylethylamine → (2S,3S)-[2-(2-{2-[(azetidine-1-carbonyl)-amino]-5-trifluoromethyl-benzoylamino}-acetylamino)-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl ester

HRID 251317ノート

反応式

HRID 251317 の反応式
[CH2:1]([O:8][C:9](=[O:19])[NH:10][CH2:11][C@H:12]([NH2:18])[C@@H:13]([OH:17])[C:14]#[C:15][CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[N:29]1([C:33]([NH:35][C:36]2[CH:48]=[CH:47][C:46]([C:49]([F:52])([F:51])[F:50])=[CH:45][C:37]=2[C:38]([NH:40][CH2:41][C:42](O)=[O:43])=[O:39])=[O:34])[CH2:32][CH2:31][CH2:30]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:19])[NH:10][CH2:11][C@H:12]([NH:18][C:42](=[O:43])[CH2:41][NH:40][C:38](=[O:39])[C:37]1[CH:45]=[C:46]([C:49]([F:51])([F:52])[F:50])[CH:47]=[CH:48][C:36]=1[NH:35][C:33]([N:29]1[CH2:32][CH2:31][CH2:30]1)=[O:34])[C@@H:13]([OH:17])[C:14]#[C:15][CH3:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21991185{2-[(Azetidine-1-carbonyl)-amino]-5-trifluoromethyl-benzoylamino}-acetic acidHCID 69196343(2S,3S)-2-amino-3-hydroxy-hex-4-ynyl-carbamic acid benzyl ester

生成物 1

HCID 69198306(2S,3S)-[2-(2-{2-[(azetidine-1-carbonyl)-amino]-5-trifluoromethyl-benzoylamino}-acetylamino)-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl ester収率 63.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

(2S,3S)-(2-Amino-3-hydroxy-hex-4-ynyl)-carbamic acid benzyl ester (520 mg, prepared as in WO PCT 0250019) was dissolved in CH2Cl2 (20 ml) and DIEA (0.74 ml) and cooled to 0° C. prior to the addition of {2-[(azetidine-1-carbonyl)-amino]-5-trifluoromethyl-benzoylamino}-acetic acid (684 mg, prepared as in WO PCT 0250019) and HATU (756 mg). After the reaction was stirred overnight at room temperature, the CH2Cl2 was removed and EtOAc was added. The organic layer was washed with saturated NH4Cl solution (aq) brine, dried, filtered, and concentrated. Flashed chromatography of the resulting residue gave (2S,3S)-[2-(2-{2-[(azetidine-1-carbonyl)-amino]-5-trifluoromethyl-benzoylamino}-acetylamino)-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl ester (745 mg). MS found: (M+H)+=590.

後処理

  1. customthe CH2Cl2 was removed
  2. additionEtOAc was added
  3. washThe organic layer was washed with saturated NH4Cl solution (aq) brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-49e1a9a2ed724a38bf4c814f6aa9155c
出典データセット
uspto-grants-2011_01
特許番号
US07863333B2

反応ノート

読み込み中…