1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (1R*,2R*)-4-benzyloxymethyl-N1-[(5-chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine

HRID 546510ノート

反応式

HRID 546510 の反応式
[CH2:1]([O:8][CH2:9][CH:10]1[CH2:14][C@@H:13]([NH:15][C:16]([C:18]2[NH:19][C:20]3[C:25]([CH:26]=2)=[CH:24][C:23]([Cl:27])=[CH:22][CH:21]=3)=[O:17])[C@H:12]([NH2:28])[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:29][N:30]1[CH2:35][CH2:34][C:33]2[N:36]=[C:37]([C:39]([O-])=[O:40])[S:38][C:32]=2[CH2:31]1.[Li+].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[CH2:1]([O:8][CH2:9][CH:10]1[CH2:14][C@@H:13]([NH:15][C:16]([C:18]2[NH:19][C:20]3[C:25]([CH:26]=2)=[CH:24][C:23]([Cl:27])=[CH:22][CH:21]=3)=[O:17])[C@H:12]([NH:28][C:39]([C:37]2[S:38][C:32]3[CH2:31][N:30]([CH3:29])[CH2:35][CH2:34][C:33]=3[N:36]=2)=[O:40])[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

6

反応物 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 23704331Lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylateHCID 58822261(1R*,2R*)-4-Benzyloxymethyl-N1-[(5-chloroindol-2-yl)carbonyl]-1,2-cyclopentanediamine

生成物 1

HCID 68905458(1R*,2R*)-4-benzyloxymethyl-N1-[(5-chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine収率 30.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

(1R*,2R*)-4-Benzyloxymethyl-N1-[(5-chloroindol-2-yl)carbonyl]-1,2-cyclopentanediamine (794 mg) was dissolved in N,N-dimethylformamide (150 ml), and lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate (694 mg), 1-hydroxybenzotriazole monohydrate (61 mg) and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (1.15 g) were added to stir the mixture overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and water was added to the residue to conduct extraction with dichloromethane. The resultant organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by preparative thin-layer chromatography (dichloromethane:acetone=2:1) to obtain Stereoisomer A (378 mg) and Stereoisomer B (354 mg) of (1R*,2R*)-4-benzyloxymethyl-N1-[(5-chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine.

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and water
  2. additionwas added to the residue
  3. extractionextraction with dichloromethane
  4. dry with materialThe resultant organic layer was dried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe residue was purified by preparative thin-layer chromatography (dichloromethane:acetone=2:1)

出典と根拠

ORDレコード
ord-e0e464dcb849476a89d978815d9f15e4
出典データセット
uspto-grants-2011_05
特許番号
US07935824B2

反応ノート

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