tert-Butyl methyl [(3R,4S,5S)-1-(3-{[(3-{[(benzyloxy)carbonyl]amino}-7-morpholin-4-ylquinolin-2-yl)carbonyl]amino}pyridin-4-yl)-5-methylpiperidine-3, 4-diyl]biscarbamate → Methyl [(3R,4S,5S)-3-amino-1-(3-{[(3-amino-7-morpholin-4-ylquinolin-2-yl)carbonyl]amino}pyridin-4-yl)-5-methylpiperidin-4-yl]carbamate

HRID 924526Notes

Reaction equation

HRID 924526 reaction equation
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]([N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]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]([N:22]4[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)=[CH:18][CH:19]=3)[N:14]=2)=[O:29])[CH2:38]1

Participants

5

Reactant 1

HCID 86726964tert-Butyl methyl [(3R,4S,5S)-1-(3-{[(3-{[(benzyloxy)carbonyl]amino}-7-morpholin-4-ylquinolin-2-yl)carbonyl]amino}pyridin-4-yl)-5-methylpiperidine-3, 4-diyl]biscarbamate

Product 1

HCID 86726965Methyl [(3R,4S,5S)-3-amino-1-(3-{[(3-amino-7-morpholin-4-ylquinolin-2-yl)carbonyl]amino}pyridin-4-yl)-5-methylpiperidin-4-yl]carbamateYield 52.8%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl methyl [(3R,4S,5S)-1-(3-{[(3-{[(benzyloxy)carbonyl]amino}-7-morpholin-4-ylquinolin-2-yl)carbonyl]amino}pyridin-4-yl)-5-methylpiperidine-3,4-diyl]biscarbamate (30 mg, 0.039 mmol) in MeOH (2.0 mL) and THF (1.0 mL), 10% Pd on carbon (6.9 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 90 min. The mixture was then filtered and 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 1 h, 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 (11 mg, 52%). LCMS calc. for C27H35N8O4 (M+H)+: m/z=535.3. Found: 535.4.

Workup

  1. customThe reaction mixture was deoxygenated under reduced pressure and hydrogen
  2. additionwas introduced via a balloon
  3. filtrationThe mixture was then filtered
  4. concentrationconcentrated 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 1 h
  8. concentrationconcentrated 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)

Sources & evidence

ORD record
ord-e78bcb0b91eb440fad2054420edf64b7
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

Loading…