Diisopropylethylamine → 10-[(2'-Methoxy-2-methyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid (2,3-dihydroxy-propyl)-methyl-amide

HRID 2184447ノート

反応式

HRID 2184447 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15]([N:17]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[CH2:21][N:20]3[C:28]([C:31](O)=[O:32])=[CH:29][CH:30]=[C:19]3[CH2:18]2)=[O:16])=[CH:11][C:10]=1[CH3:34].[CH3:35][NH:36][CH2:37][CH:38](O)[CH2:39][OH:40].[OH2:42].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[OH:42][CH:38]([CH2:39][OH:40])[CH2:37][N:36]([CH3:35])[C:31]([C:28]1[N:20]2[C:19]([CH2:18][N:17]([C:15]([C:12]3[CH:13]=[CH:14][C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[C:10]([CH3:34])[CH:11]=3)=[O:16])[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[CH2:21]2)=[CH:30][CH:29]=1)=[O:32]

参加物

8

反応物 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27341223-(Methylamino)propane-1,2-diolHCID 27960291-Hydroxybenzotriazole hydrateHCID 1027581310-[(2'-methoxy-2-methyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid

生成物 1

HCID 1018714110-[(2'-Methoxy-2-methyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid (2,3-dihydroxy-propyl)-methyl-amide収率 18.5%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 10-[(2′-methoxy-2-methyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H— pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Step E (0.50 g, 1.10 mmol) and 3-methylamino-1,2-propanediol (0.14 mL, 1.33 mmol) in N,N-dimethylformamide (4 mL) was added 1-hydroxybenzotriazole monohydrate (0.16 g, 1.18 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.23 g, 1.20 mmol) followed by N,N-diisopropylethyl amine (0.29 mL, 1.66 mmol). The reaction mixture was stirred overnight, diluted with ethyl acetate and washed with water and saturated aqueous sodium bicarbonate. The organic phase was then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow oil. Purification by flash chromatography using a solvent system of 3% methanol in chloroform gave a white foam which was crystallized by trituration with diethyl ether-hexane to provide 0.11 g of title product as a white amorphous solid.

後処理

  1. washwashed with water and saturated aqueous sodium bicarbonate
  2. dry with materialThe organic phase was then dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a yellow oil
  6. customPurification by flash chromatography
  7. customgave a white foam which
  8. customwas crystallized by trituration with diethyl ether-hexane

出典と根拠

ORDレコード
ord-420fc6aa00494360b76ab850ae58a020
出典データセット
uspto-grants-2005_05
特許番号
US06900200B2

反応ノート

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