Triethylamine → 4-{(1R)-1-[(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl]-2-(2-naphthyl)ethylcarbamoyl}piperidine-1-carboxylic acid tertbutyl ester

HRID 849830ノート

反応式

HRID 849830 の反応式
Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([C:37]([OH:39])=O)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].Cl.[NH2:41][C@H:42]([CH2:60][C:61]1[CH:70]=[CH:69][C:68]2[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=2)[CH:62]=1)[C:43]([NH:45][C@@H:46]([C:54]1[O:58][N:57]=[C:56]([CH3:59])[N:55]=1)[CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:44].C(N(CC)CC)C>CN(C)C=O>[C:24]([O:28][C:29]([N:31]1[CH2:32][CH2:33][CH:34]([C:37](=[O:39])[NH:41][C@@H:42]([C:43](=[O:44])[NH:45][C@@H:46]([C:54]2[O:58][N:57]=[C:56]([CH3:59])[N:55]=2)[CH2:47][C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH2:60][C:61]2[CH:70]=[CH:69][C:68]3[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=3)[CH:62]=2)[CH2:35][CH2:36]1)=[O:30])([CH3:25])([CH3:26])[CH3:27]

参加物

7

反応物 5

HCID 8471TriethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 69834587(2R)-2-amino-N-[(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethyl]-3-(2-naphthyl)propionamide hydrochloride

生成物 1

HCID 544782074-{(1R)-1-[(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl]-2-(2-naphthyl)ethylcarbamoyl}piperidine-1-carboxylic acid tertbutyl ester収率 87.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.92 g, 4.82 mmol) and 1-hydroxybenzotriazole monohydrate (0.74 g, 4.83 mmol) were added to a solution of N-tertbutoxycarbonyl-4-piperidine carboxylic acid (1.10 g, 4.80 mmol) in N,N-dimethylformamide (15 ml). After 30 min at 20° C. a mixture of (2R)-2-amino-N-[(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethyl]-3-(2-naphthyl)propionamide hydrochloride (1.50 g, 3.43 mmol) and triethylamine (0.35 g, 3.46 mmol) in N,N-dimethylformamide (15 ml) were added. After 18 h at 20° C. the reaction mixture was poured on ice water (180 ml) and extracted several times with ethyl acetate (total 180 ml). The organic phases were collected and washed with aqueous citric acid (10%, 25 ml), a saturated solution of sodium hydrogencarbonate (3×25 ml) and water (3×25 ml). After drying (magnesium sulfate) the solution was concentrated in vacuo and crystallized from ethyl acetate to give 1.84 g of 4-{(1R)-1-[(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl]-2-(2-naphthyl)ethylcarbamoyl}piperidine-1-carboxylic acid tertbutyl ester.

後処理

  1. additionwere added
  2. additionAfter 18 h at 20° C. the reaction mixture was poured on ice water (180 ml)
  3. extractionextracted several times with ethyl acetate (total 180 ml)
  4. customThe organic phases were collected
  5. washwashed with aqueous citric acid (10%, 25 ml)
  6. dry with materialAfter drying (magnesium sulfate) the solution
  7. concentrationwas concentrated in vacuo
  8. customcrystallized from ethyl acetate

出典と根拠

ORDレコード
ord-8d6e9cb28abe48c9936b3994cef925b3
出典データセット
uspto-grants-2000_01
特許番号
US06013658

反応ノート

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