Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate → tert-Butyl (1S,2R)-2-(4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

HRID 2092764ノート

反応式

HRID 2092764 の反応式
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[CH:25]=[C:24]([C:26]#[N:27])[C:19]([C:20]([O:22]C)=O)=[C:18]([C:28]2[CH:29]=[N:30][N:31]([CH3:33])[CH:32]=2)[N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>[Pd].CO.CC(O)=O>[CH3:33][N:31]1[CH:32]=[C:28]([C:18]2[C:19]3[C:20](=[O:22])[NH:27][CH2:26][C:24]=3[CH:25]=[C:16]([NH:15][C@@H:10]3[CH2:11][CH2:12][CH2:13][CH2:14][C@@H:9]3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])[N:17]=2)[CH:29]=[N:30]1

参加物

5

反応物 1

HCID 67237740Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate

生成物 1

HCID 86654709tert-Butyl (1S,2R)-2-(4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate収率 58.1%

試薬・触媒・溶媒 3

HCID 23938Palladium触媒HCID 176Acetic Acid溶媒HCID 887Methanol溶媒

実験手順

A solution of methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate (110 mg, 0.242 mmol) and palladium on carbon (2.58 mg, 0.024 mmol) in MeOH (5 mL) and HOAc (1 mL) was stirred at RT overnight under H2 atmosphere. After reaction, the mixture was filtered through Celite, the filtrate was evaporated, and the residue was diluted with MeOH and sat aq NaHCO3. The mixture was stirred at RT for 30 min and extracted with EtOAc. The organic phase was washed with brine, dried over MgSO4, and evaporated. The residue was purified by chromatography on SiO2 and preparative HPLC to give the title compound (60 mg, 58.1%). 1H NMR (500 MHz, CDCl3) δ ppm 1.26-1.87 (m, 17H), 3.91 (s, 3H), 4.25 (br s, 2H), 5.16-5.49 (m 2H), 6.23 (br s, 1H), 6.75 (br s, 1H), 8.18-8.44 (m, 1H), 8.76-9.05 (m, 1H).

後処理

  1. customAfter reaction
  2. filtrationthe mixture was filtered through Celite
  3. customthe filtrate was evaporated
  4. additionthe residue was diluted with MeOH
  5. extractionextracted with EtOAc
  6. washThe organic phase was washed with brine
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. customThe residue was purified by chromatography on SiO2 and preparative HPLC

出典と根拠

ORDレコード
ord-be1a6930a70c4e21b804d9281a8f7276
出典データセット
uspto-grants-2013_05
特許番号
US08440689B2

反応ノート

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