Pyridine → N4-[2-(3-tert-Butoxycarbonylaminopropoxy)-4-methoxybenzoyl]-N3-(4-methoxybenzoyl)-3,4-pyridinediamine

HRID 1445443Notes

Reaction equation

HRID 1445443 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:14]=1[C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[CH3:30][O:31][C:32]1[CH:47]=[CH:46][C:35]([C:36]([NH:38][C:39]2[CH:40]=[N:41][CH:42]=[CH:43][C:44]=2[NH2:45])=[O:37])=[CH:34][CH:33]=1.N1C=CC=CC=1>ClCCl.CC=C(C)C.C(Cl)(Cl)Cl.CN(C=O)C>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:14]=1[C:15]([NH:45][C:44]1[CH:43]=[CH:42][N:41]=[CH:40][C:39]=1[NH:38][C:36](=[O:37])[C:35]1[CH:34]=[CH:33][C:32]([O:31][CH3:30])=[CH:47][CH:46]=1)=[O:17])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 12069538N3-(4-methoxybenzoyl)-3,4-pyridinediamineHCID 685323072-(3-Tert-butoxycarbonylaminopropoxy)-4-methoxybenzoic acid

Product 1

HCID 69492866N4-[2-(3-tert-Butoxycarbonylaminopropoxy)-4-methoxybenzoyl]-N3-(4-methoxybenzoyl)-3,4-pyridinediamineYield 80%

Reagents, catalysts & solvents 4

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 105532-Methyl-2-buteneSolvent

Procedure

2-(3-tert-Butoxycarbonylaminopropoxy)-4-methoxybenzoic acid (1.6 g, 4.94 mmol) was dissolved in dry dichloromethane (20 mL) and DMF (0.5 mL) under nitrogen atmosphere. Oxalyl chloride (0.475 mL, 5.43 mmol) was added via syringe. Vigorous bubbling occurred. The mixture was stirred until gas evolution ceased, then concentrated in vacuo. The residue was dissolved in amylene-stabilized chloroform (20 mL), transferred to an addition funnel, then added dropwise over 2 hours to an ice cold solution of N3-(4-methoxybenzoyl)-3,4-pyridinediamine (1.0 g, 4.11 mmol) in amylene-stabilized chloroform (30 mL) and pyridine (2 mL, 24.7 mmol). The mixture was allowed to warm to room temperature and stir for 2.5 days. The resulting slurry was diluted with dichloromethane (50 mL) and washed twice with saturated NaHCO3, once with brine, then dried and concentrated in vacuo. Purification on a 6 mm chromatotron rotor with isocratic 96:3:1 CHCl3:MeOH:triethylamine yielded about 80% pure material that was carried on directly.

Workup

  1. customVigorous bubbling
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in amylene-
  4. customtransferred to an addition funnel
  5. stirringstir for 2.5 days
  6. washwashed twice with saturated NaHCO3, once with brine
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customPurification on a 6 mm chromatotron rotor with isocratic 96:3:1 CHCl3

Sources & evidence

ORD record
ord-ac31763e391042a1beff7a08a60e53e9
Source dataset
uspto-grants-2010_02
Patent number
US07666866B2

Reaction notes

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