Diisopropylamine → ((S)-1-Cyclohexyl-2-{(S)-2-[2-(2,3-dihydro-indol-1-yl)-pyridin-4-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-carbamic acid tert-butyl ester

HRID 1667619ノート

反応式

HRID 1667619 の反応式
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:53]1[CH2:57][CH2:56][CH2:55][C@H:54]1[C:58]1[CH:63]=[CH:62][N:61]=[C:60]([N:64]2[C:72]3[C:67](=[CH:68][CH:69]=[CH:70][CH:71]=3)[CH2:66][CH2:65]2)[CH:59]=1.C(NC(C)C)(C)C>CN(C=O)C.O>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([N:53]1[CH2:57][CH2:56][CH2:55][C@H:54]1[C:58]1[CH:63]=[CH:62][N:61]=[C:60]([N:64]2[C:72]3[C:67](=[CH:68][CH:69]=[CH:70][CH:71]=3)[CH2:66][CH2:65]2)[CH:59]=1)=[O:12])([CH3:2])([CH3:3])[CH3:4]

参加物

8

反応物 5

HCID 7912DiisopropylamineHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycineHCID 581119321-((S)-4-pyrrolidin-2-yl-pyridin-2-yl)-2,3-dihydro-1H-indole

生成物 1

HCID 66889172((S)-1-Cyclohexyl-2-{(S)-2-[2-(2,3-dihydro-indol-1-yl)-pyridin-4-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-carbamic acid tert-butyl ester収率 68%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

実験手順

A solution of (S)-tert-butoxycarbonylamino-cyclohexyl-acetic acid (99 mg, 0.39 mmol), HOBt (57 mg, 0.42 mmol) and HBTU (160 mg, 0.42 mmol) in DMF (10 mL) is stirred at room temperature for 30 min. Then a solution of 1-((S)-4-pyrrolidin-2-yl-pyridin-2-yl)-2,3-dihydro-1H-indole (6) in DMF (10 mL) is added, followed by diisopropylamine (226 mg, 1.75 mmol). After stirring at room temperature for 2 h, the reaction mixture is diluted with water and extracted with EtOAc. The combined organic layers are washed with water, sat. NaHCO3, brine, dried over Na2SO4, filtered and concentrated down. The crude product is purified by flash chromatography on silica gel (EtOAc/Hexane: 5%˜40%) to give ((S)-1-Cyclohexyl-2-{(S)-2-[2-(2,3-dihydro-indol-1-yl)-pyridin-4-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-carbamic acid tert-butyl ester as white solid (120 mg, 68%). M/Z=505.3 [M+1]

後処理

  1. extractionextracted with EtOAc
  2. washThe combined organic layers are washed with water, sat. NaHCO3, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated down
  6. customThe crude product is purified by flash chromatography on silica gel (EtOAc/Hexane: 5%˜40%)

出典と根拠

ORDレコード
ord-ff5c1cc04cb443eea9d63bc7bbdc24de
出典データセット
uspto-grants-2011_10
特許番号
US08044209B2

反応ノート

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