tert-Butyl methyl {(3R,4S,5S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(3,6-dihydro-2H-pyran-4-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidine-3, 4-diyl}biscarbamate → Methyl {(3R,4S,5S)-3-amino-1-[3-({[3-amino-7-(tetrahydro-2H-pyran-4-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidin-4-yl}carbamate

HRID 924530ノート

反応式

HRID 924530 の反応式
C(OC([NH:11][C:12]1[C:13]([C:28]([NH:30][C:31]2[CH:32]=[N:33][CH:34]=[CH:35][C:36]=2[N:37]2[CH2:42][C@H:41]([CH3:43])[C@H:40]([NH:44][C:45](=[O:48])[O:46][CH3:47])[C@H:39]([NH:49]C(=O)OC(C)(C)C)[CH2:38]2)=[O:29])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([C:22]1[CH2:23][CH2:24][O:25][CH2:26][CH:27]=1)[CH:16]=2)=O)C1C=CC=CC=1>CO.C1COCC1.[Pd]>[NH2:49][C@H:39]1[C@@H:40]([NH:44][C:45](=[O:48])[O:46][CH3:47])[C@@H:41]([CH3:43])[CH2:42][N:37]([C:36]2[CH:35]=[CH:34][N:33]=[CH:32][C:31]=2[NH:30][C:28]([C:13]2[C:12]([NH2:11])=[CH:21][C:20]3[C:15](=[CH:16][C:17]([CH:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[CH:18][CH:19]=3)[N:14]=2)=[O:29])[CH2:38]1

参加物

5

反応物 1

HCID 86726968tert-Butyl methyl {(3R,4S,5S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(3,6-dihydro-2H-pyran-4-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidine-3, 4-diyl}biscarbamate

生成物 1

HCID 86726969Methyl {(3R,4S,5S)-3-amino-1-[3-({[3-amino-7-(tetrahydro-2H-pyran-4-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidin-4-yl}carbamate収率 59.4%

試薬・触媒・溶媒 3

HCID 23938Palladium触媒HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of tert-butyl methyl {(3R,4S,5S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(3,6-dihydro-2H-pyran-4-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidine-3,4-diyl}biscarbamate (63 mg, 0.082 mmol) in MeOH (2.0 mL) and THF (1.0 mL), 10% Pd on carbon (16 mg) was added. The reaction mixture was deoxygenated under reduced pressure and hydrogen was introduced via a balloon. The reaction mixture was stirred at room temperature under hydrogen for 20 h. The mixture was filtered and the filtrate concentrated under reduced pressure. The resulting residue was dissolved in DCM (2 mL), and TFA (2 mL) was added. The mixture was stirred at room temperature for 30 min. then concentrated under reduced pressure. The residue was purified by preparative LCMS (pH=10 method; XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH) to give the title compound as a yellow powder (26 mg, 58%). LCMS calc. for C28H36N7O4 (M+H)+: m/z=534.3. Found: 534.4.

後処理

  1. customThe reaction mixture was deoxygenated under reduced pressure and hydrogen
  2. additionwas introduced via a balloon
  3. filtrationThe mixture was filtered
  4. concentrationthe filtrate concentrated under reduced pressure
  5. dissolutionThe resulting residue was dissolved in DCM (2 mL)
  6. additionTFA (2 mL) was added
  7. stirringThe mixture was stirred at room temperature for 30 min.
  8. concentrationthen concentrated under reduced pressure
  9. customThe residue was purified by preparative LCMS (pH=10 method
  10. washXBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH)

出典と根拠

ORDレコード
ord-d0bb600eb5694d45bf5cccab1d8fcb81
出典データセット
uspto-grants-2016_03
特許番号
US09278950B2

反応ノート

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