Diisopropylethylamine → HCID 22346264, compound

HRID 897323Notes

Reaction equation

HRID 897323 reaction equation
[F:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19]([O:20][CH3:21])=[C:18]3C(C=C[CH:16]=[N:17]3)=[C:12]([NH:22][CH3:23])[N:11]=2)=[O:9])=[CH:4][CH:3]=1.[CH:26]([N:29]([CH:32]([CH3:34])[CH3:33])[CH2:30][CH3:31])(C)C.ClC(Cl)([O:38]C(=O)OC(Cl)(Cl)Cl)Cl.[O:47]1[CH2:52][CH2:51][N:50](CCN)[CH2:49][CH2:48]1>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[N:22]([CH3:23])[C:26](=[O:38])[N:29]([CH2:30][CH2:31][N:50]4[CH2:51][CH2:52][O:47][CH2:48][CH2:49]4)[C:32]4=[CH:34][CH:16]=[N:17][C:18]([C:19]=2[O:20][CH3:21])=[C:33]34)=[O:9])=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 94429Triphosgene2×HCID 4082852-MorpholinoethylamineHCID 22346362HCID 22346362, compound

Product 1

HCID 22346264HCID 22346264, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N-(4-fluorobenzyl)-8-methoxy-5-(methylamino)-1,6-naphthyridine-7-carboxamide (504 mg, 1.48 mmol) in CH2Cl2 (5 mL) at OC was added diisopropylethylamine (0.77 mL, 4.4 mmol) and triphosgene (0.22 g, 0.74 mmol) and the mixture was stirred at room temperature for 16 hr. Additional diisopropylethylamine (0.77 mL, 4.4 mmol) and triphosgene (0.22 g, 0.74 mmol) was added and the reaction was stirred an additional 16 hr at room temperature. The reaction was diluted with CH2Cl2 and a portion of this solution (1.0 mL) was treated with 2-morpholinoethylamine (0.12 mL 0.89 mmol) at room temperature for 16 hr. The solvent was evaporated in vacuo and the residue dissolved in DMSO (0.5 mL) and purified by reverse phase HPLC. (Vydak C18, Gradient elution with Water:Acetonitrile 95:5 to 5:95 with 0.1% TFA at 30 mL/min over 15 mins). Lyophilization of the pure fractions afforded the title compound as an off white solid which was used directly in step 2.

Workup

  1. stirringthe reaction was stirred an additional 16 hr at room temperature
  2. customThe solvent was evaporated in vacuo
  3. dissolutionthe residue dissolved in DMSO (0.5 mL)
  4. custompurified by reverse phase HPLC
  5. wash(Vydak C18, Gradient elution with Water:Acetonitrile 95:5 to 5:95 with 0.1% TFA at 30 mL/min over 15 mins)

Sources & evidence

ORD record
ord-12d00f3e82e94fde9c26af620a0c2a68
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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