Diisopropylethylamine → 4-Cyclobutylmethoxy-1H-indole-2-carboxylic acid {4-hydroxy-4-[2-((3S,4S)-4-hydroxy-3-methyl-piperidin-1-yl)-ethyl]-cyclohexyl}-amide

HRID 1804795ノート

反応式

HRID 1804795 の反応式
[CH:1]1([CH2:5][O:6][C:7]2[CH:15]=[CH:14][CH:13]=[C:12]3[C:8]=2[CH:9]=[C:10]([C:16]([OH:18])=O)[NH:11]3)[CH2:4][CH2:3][CH2:2]1.[NH2:19][CH:20]1[CH2:25][CH2:24][C:23]([CH2:27][CH2:28][N:29]2[CH2:34][CH2:33][C@H:32]([OH:35])[C@@H:31]([CH3:36])[CH2:30]2)([OH:26])[CH2:22][CH2:21]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[OH:26][C:23]1([CH2:27][CH2:28][N:29]2[CH2:34][CH2:33][C@H:32]([OH:35])[C@@H:31]([CH3:36])[CH2:30]2)[CH2:24][CH2:25][CH:20]([NH:19][C:16]([C:10]2[NH:11][C:12]3[C:8]([CH:9]=2)=[C:7]([O:6][CH2:5][CH:1]2[CH2:2][CH2:3][CH2:4]2)[CH:15]=[CH:14][CH:13]=3)=[O:18])[CH2:21][CH2:22]1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59152645HCID 59152645、化合物HCID 591526824-Cyclobutylmethoxy-1H-indole-2-carboxylic acid

生成物 1

HCID 591526544-Cyclobutylmethoxy-1H-indole-2-carboxylic acid {4-hydroxy-4-[2-((3S,4S)-4-hydroxy-3-methyl-piperidin-1-yl)-ethyl]-cyclohexyl}-amide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of 4-cyclobutylmethoxy-1H-indole-2-carboxylic acid (16a) (140 mg, 0.383 mmol), (3S,4S)-1-[2-(4-amino-1-hydroxy-cyclohexyl)-ethyl]-3-methyl-piperidin-4-ol (14) (103 mg, 0.421 mmol) and DIEA (0.263 ml, 1.532 mmol) in 5 ml of DMF is treated with solid TBTU (139 mg, 0.421 mmol). The mixture is stirred for 2 h at rt and then evaporated. The crude residue is dissolved in EtOAc and extracted with 1M-HCl. The aqueous layer is separated, its pH adjusted to 14 and extracted 3-times with DCM. The organic layers are dried over sodium sulphate and evaporated. The crude product is then purified by chromatography on silicagel using methanol and DCM (saturated with ammonia) from 1:99 to 5:95.

後処理

  1. customevaporated
  2. dissolutionThe crude residue is dissolved in EtOAc
  3. extractionextracted with 1M-HCl
  4. customThe aqueous layer is separated
  5. extractionextracted 3-times with DCM
  6. dry with materialThe organic layers are dried over sodium sulphate
  7. customevaporated
  8. customThe crude product is then purified by chromatography on silicagel

出典と根拠

ORDレコード
ord-a91f42adc7b5434cbdd9d13d74296632
出典データセット
uspto-grants-2013_01
特許番号
US08354431B2

反応ノート

読み込み中…