tert-Butyl methyl {(3R,4S,5S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(4-methylpiperazin-1-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-(4-methylpiperazin-1-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidin-4-yl}carbamate

HRID 924528Notes

Reaction equation

HRID 924528 reaction equation
C(OC([NH:11][C:12]1[C:13]([C:29]([NH:31][C:32]2[CH:33]=[N:34][CH:35]=[CH:36][C:37]=2[N:38]2[CH2:43][C@H:42]([CH3:44])[C@H:41]([NH:45][C:46](=[O:49])[O:47][CH3:48])[C@H:40]([NH:50]C(=O)OC(C)(C)C)[CH2:39]2)=[O:30])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([N:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1)[CH:16]=2)=O)C1C=CC=CC=1>CO.[Pd]>[NH2:50][C@H:40]1[C@@H:41]([NH:45][C:46](=[O:49])[O:47][CH3:48])[C@@H:42]([CH3:44])[CH2:43][N:38]([C:37]2[CH:36]=[CH:35][N:34]=[CH:33][C:32]=2[NH:31][C:29]([C:13]2[C:12]([NH2:11])=[CH:21][C:20]3[C:15](=[CH:16][C:17]([N:22]4[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]4)=[CH:18][CH:19]=3)[N:14]=2)=[O:30])[CH2:39]1

Participants

4

Reactant 1

HCID 86726966tert-Butyl methyl {(3R,4S,5S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(4-methylpiperazin-1-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidine-3, 4-diyl}biscarbamate

Product 1

HCID 86726967Methyl {(3R,4S,5S)-3-amino-1-[3-({[3-amino-7-(4-methylpiperazin-1-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidin-4-yl}carbamateYield 66.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of tert-butyl methyl {(3R,4S,5S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(4-methylpiperazin-1-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidine-3,4-diyl}biscarbamate (62 mg, 0.080 mmol) in MeOH (3.0 mL), 10% Pd on carbon (15 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 the hydrogen balloon for 1 h. The mixture was filtered and concentrated under reduced pressure. The resulting residue was dissolved in DCM (2 mL), and TFA (2 mL) was added. The resulting 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 (29 mg, 65%). LCMS calc. for C28H38N9O3 (M+H)+: m/z=548.3. Found: 548.4.

Workup

  1. customThe reaction mixture was deoxygenated under reduced pressure and hydrogen
  2. additionwas introduced via a balloon
  3. filtrationThe mixture was filtered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe resulting residue was dissolved in DCM (2 mL)
  6. additionTFA (2 mL) was added
  7. stirringThe resulting 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-34a163652b414c2a86836d6e3b09654a
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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