6-Formyl-4-isopropoxy-[1,5]naphthyridine-3-carbonitrile → 6-(2-amino-4-oxo-4H-thiazol-5-ylidenemethyl)-4-isopropoxy-[1,5]naphthyridine-3-carbonitrile

HRID 968710Notes

Reaction equation

HRID 968710 reaction equation
COC1C=CC(/C=[C:16]2/[C:17]([NH:19][C:20]([S:22]/2)=[NH:21])=[O:18])=CC=1OC1CCCC1.C(O[Na])(C)=O.[CH:28]([C:30]1[N:31]=[C:32]2[C:37](=[CH:38][CH:39]=1)[N:36]=[CH:35][C:34]([C:40]#[N:41])=[C:33]2[O:42][CH:43]([CH3:45])[CH3:44])=O>CC(O)=O>[NH2:21][C:20]1[S:22][C:16](=[CH:28][C:30]2[N:31]=[C:32]3[C:37](=[CH:38][CH:39]=2)[N:36]=[CH:35][C:34]([C:40]#[N:41])=[C:33]3[O:42][CH:43]([CH3:45])[CH3:44])[C:17](=[O:18])[N:19]=1

Participants

5

Reactant 3

HCID 587243116-Formyl-4-isopropoxy-[1,5]naphthyridine-3-carbonitrileHCID 137629131(5Z)-5-[(3-cyclopentyloxy-4-methoxyphenyl)methylidene]-2-imino-1,3-thiazolidin-4-oneHCID 178418247HCID 178418247, compound

Product 1

HCID 686174026-(2-amino-4-oxo-4H-thiazol-5-ylidenemethyl)-4-isopropoxy-[1,5]naphthyridine-3-carbonitrileYield 22.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of pseudothiohydantoin (Aldrich, 97%, 23.2 mg, 0.20 mmol), AcONa (160 mg, 1.95 mmol), molecular sieves, and 6-formyl-4-isopropoxy-[1,5]naphthyridine-3-carbonitrile (53.1 mg, 0.22 mmol) (prepared as described below) in a sealed tube was added AcOH (0.3 mL). The reaction mixture was heated to 85-95° C. for 1.5 h. The reaction mixture was then cooled to r.t. and triturated with water. The solid was collected by filtration and washed with water. The solid was then suspended in hot DMF (20 mL) and filtered again. The filtrate was concentrated to give a brown solid: 55.8 mg, which was then purified by Biotage flash column (1%-6% MeOH in CH2Cl2) to give 6-(2-amino-4-oxo-4H-thiazol-5-ylidenemethyl)-4-isopropoxy-[1,5]naphthyridine-3-carbonitrile as a yellowish solid (15.5 mg, 22.8%). HR-ES (+) m/e calcd for C16H13N5O2S (M+H)+ 340.0863. found 340.0863.

Workup

  1. temperatureThe reaction mixture was then cooled to r.t.
  2. customtriturated with water
  3. filtrationThe solid was collected by filtration
  4. washwashed with water
  5. filtrationfiltered again
  6. concentrationThe filtrate was concentrated
  7. customto give a brown solid
  8. custom55.8 mg, which was then purified by Biotage flash column (1%-6% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-b5c492fd923b463e9465f4878bb8c30d
Source dataset
uspto-grants-2007_12
Patent number
US07304074B2

Reaction notes

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