Phosgene → HCID 58997019, compound

HRID 251176Notes

Reaction equation

HRID 251176 reaction equation
[CH3:1][C:2]1[C:3]([CH2:8][N:9]([CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:4][CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.[C:33](Cl)(Cl)=[O:34].[NH2:37][NH2:38].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>C1(C)C=CC=CC=1.C1COCC1.CCN(CC)CC>[CH3:1][C:2]1[C:3]([CH2:8][N:9]([CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH:10]2[CH2:15][CH2:14][N:13]([C:33]([NH:37][NH2:38])=[O:34])[CH2:12][CH2:11]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 6371Phosgene2×HCID 9321HydrazineHCID 81531Diisopropylethylamine2×HCID 90495Di-tert-butyl dicarbonateHCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 58997019HCID 58997019, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a 0° C. solution of COMPOUND 249 (106 mg, 0.341 mmol) in toluene (5 mL) and DIPEA (0.12 mL, 0.68 mmol) was added phosgene solution in toluene (20 wt %, 0.185 mL, 0.375 mmol). After one hour the TLC of the reaction mixture showed that starting material was still present, and additional phosgene solution (0.050 mL) and DIPEA (0.100 mL) were added. After 30 min, excess anhydrous hydrazine (0.2 mL) was added and the mixture was warmed to room temperature and was stirred for 30 minutes. Reaction mixture was concentrated under reduced pressure and the residue was purified by radial chromatography (19:1:0.1 CH2Cl2:MeOH:NH4OH) on silica gel twice, however complete purification was not achieved. The material (41 mg, 33%, 0.103 mmol) was dissolved in THF, and Et3N (0.200 mL) and Boc2O (100 mg, 0.50 mmol) were added. The mixture was stirred at room temperature for 2 days. The solvent was removed and the crude material was purified by radial chromatography (20:1:1 CH2Cl2:MeOH:NH4OH) to provide 21 mg (43%) of mono-Boc protected product.

Workup

  1. waitAfter 30 min
  2. customReaction mixture
  3. concentrationwas concentrated under reduced pressure
  4. customthe residue was purified by radial chromatography (19:1:0.1 CH2Cl2:MeOH:NH4OH) on silica gel twice
  5. customhowever complete purification
  6. stirringThe mixture was stirred at room temperature for 2 days
  7. customThe solvent was removed
  8. customthe crude material was purified by radial chromatography (20:1:1 CH2Cl2:MeOH:NH4OH)
  9. customto provide 21 mg (43%) of mono-Boc protected product

Sources & evidence

ORD record
ord-96cf4542850046b1b8b0b259eeb7b437
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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