1-Hydroxybenzotriazole → HCID 69182599、化合物

HRID 132885

反応式

HRID 132885 の反応式
Cl.Cl.[CH2:3]([CH:5]1[C:10]2=[N:11][CH:12]=[CH:13][N:14]=[C:9]2[CH2:8][CH2:7][NH:6]1)[CH3:4].C(N(CC)C(C)C)(C)C.[C:24]([O:28][C:29]([NH:31][C@H:32]([CH2:37][C:38]1[CH:43]=[C:42]([F:44])[C:41]([F:45])=[CH:40][C:39]=1[F:46])[CH2:33][C:34](O)=[O:35])=[O:30])([CH3:27])([CH3:26])[CH3:25].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[C:24]([O:28][C:29]([NH:31][C@H:32]([CH2:37][C:38]1[CH:43]=[C:42]([F:44])[C:41]([F:45])=[CH:40][C:39]=1[F:46])[CH2:33][C:34]([N:6]1[CH2:7][CH2:8][C:9]2[C:10](=[N:11][CH:12]=[CH:13][N:14]=2)[CH:5]1[CH2:3][CH3:4])=[O:35])=[O:30])([CH3:27])([CH3:25])[CH3:26]

参加物

7

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acid2 回HCID 69193469HCID 69193469、化合物2 回

生成物 1

HCID 69182599HCID 69182599、化合物

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

5-Ethyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazine dihydrochloride (Intermediate 32, 26 mg, 0.11 mmol) was dissolved in N,N-dimethylformamide (DMF, 0.75 mL) containing N,N-diisopropylethylamine (0.046 mL, 34 mg, 0.26 mmol). (3R)-3-(tert-Butoxycarbonylamino)4 (2,4,5-trifluorophenyl)butanoic acid (Intermediate 3, 36 mg, 0.11 mmol), 1-hydroxybenzotriazole (16 mg, 0.12 mmol), and a portion of molecular sieve pellets (4 Å) were added, followed 10 min later by 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (33 mg, 0.17 mmol). After stirring for 16 h at room temperature, the mixture was partitioned between ethyl acetate (25 mL) and saturated aqueous sodium bicarbonate solution (10 mL). The organic layer was washed with saturated aqueous brine (10 mL) and the aqueous layers were extracted in succession with ethyl acetate (25 mL). The organic layers were dried over sodium sulfate, decanted, and evaporated. Purification by flash column chromatography (silica gel, 15-20% ethyl aceate/0.75-1.0% methanol/dichloromethane) gave the title compound as a mixture of diastereomers. Separation was accomplished by EPLC using a Chiralcel OJ column, eluting with 8% ethanol in hexanes. The first-eluting diastereomer was used in Step B to produce the more active final product. LC/MS: 501 (M+Na).

後処理

  1. customthe mixture was partitioned between ethyl acetate (25 mL) and saturated aqueous sodium bicarbonate solution (10 mL)
  2. washThe organic layer was washed with saturated aqueous brine (10 mL)
  3. extractionthe aqueous layers were extracted in succession with ethyl acetate (25 mL)
  4. dry with materialThe organic layers were dried over sodium sulfate
  5. customdecanted
  6. customevaporated
  7. customPurification by flash column chromatography (silica gel, 15-20% ethyl aceate/0.75-1.0% methanol/dichloromethane)

出典と根拠

ORDレコード
ord-b40d1eda35024a54b50c82d9de495a01
出典データセット
uspto-grants-2008_06
特許番号
US07388019B2

関連ノート

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