Phosgene → HCID 118036914, compound

HRID 1777846Notes

Reaction equation

HRID 1777846 reaction equation
[C:1](Cl)(Cl)=[O:2].C(N(CC)CC)C.[CH3:12][O:13][CH:14]([O:25][CH3:26])[C:15]1[N:24]=[C:23]2[C:18]([CH2:19][CH2:20][CH2:21][NH:22]2)=[CH:17][CH:16]=1.[F:27][C:28]([F:37])([F:36])[C:29]1[CH:30]=[CH:31][C:32]([NH2:35])=[N:33][CH:34]=1>C1COCC1.C([O-])(O)=O.[Na+]>[CH3:26][O:25][CH:14]([O:13][CH3:12])[C:15]1[N:24]=[C:23]2[C:18]([CH2:19][CH2:20][CH2:21][N:22]2[C:1]([NH:35][C:32]2[CH:31]=[CH:30][C:29]([C:28]([F:36])([F:27])[F:37])=[CH:34][N:33]=2)=[O:2])=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 177501767-(Dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine2×

Product 1

HCID 118036914HCID 118036914, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of phosgene (20% solution in toluene, 0.265 ml, 0.504 mmol) in THF (2 ml) was added triethylamine (0.20 ml, 1.44 mmol). Subsequently, a solution of 7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 4, 100 mg, 0.480 mmol) in THF (2 ml) was added drop wise. The resulting yellow suspension was stirred for 15 min, then 5-(trifluoromethyl)pyridin-2-amine (93 mg, 0.576 mmol) was added and the reaction mixture stirred for 2.5 days. The reaction mixture was diluted with sat. aq. NaHCO3 and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100). The product containing fractions were concentrated to give the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 13.83 (s, 1H), 8.70 (s, 1H), 8.26 (d, 1H), 8.20-8.12 (m, 1H), 7.73 (d, 1H), 7.18 (d, 1H), 5.37 (s, 1H), 4.01-3.93 (m, 2H), 3.39 (s, 6H), 2.86 (t, 2H), 1.98-1.87 (m, 2H). (UPLC-MS 1) tR 1.29 min; ESI-MS 397.0 [M+H]+.

Workup

  1. stirringthe reaction mixture stirred for 2.5 days
  2. extractionextracted twice with EtOAc
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100)
  7. additionThe product containing fractions
  8. concentrationwere concentrated

Sources & evidence

ORD record
ord-81e8643d00ad4f4db192802b0acfc42d
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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