Hydrochloric Acid → HCID 10243146, compound

HRID 375609Notes

Reaction equation

HRID 375609 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=O)[N:7]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][C:8]3=[N:9]2)=[CH:4][CH:3]=1.Cl>C(O)(=O)C.[Zn]>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][N:7]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][C:8]3=[N:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 42461193-chloro-7,8,9,10-tetrahydro-6H-azepino[2,1-b]quinazolin-12-one

Product 1

HCID 10243146HCID 10243146, compound

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 2 g of 3-chloro-7,8,9,10-tetrahydroazepino[2,1-b]quinazolin-12(6H)-one, dissolved in 50 mL of glacial acetic acid was stirred 25 g of zinc dust with vigorous mechanical stirring. The mixture was heated to 55° C.-60° C. and concentrated hydrochloric acid was added dropwise (approximately 20 mL). The reaction was checked by TLC. Usually between 20 minutes to 5 hours were required for completion. The excess zinc was filtered off, the solution concentrated in vacuo, and basified with 20% sodium hydroxide solution. The product was extracted with tetrahydrofuran. Then the free base was chromatographed using 300:25:1 CHCl3 :MeOH:28% aqueous ammonia. The corresponding fractions were combined, concentrated in vacuo, and dried in high vacuum providing the 3-chloro-6,7,8,9,10,12-hexahydroazepino[2,1-b]quinazoline as a white crystalline solid; m.p. 102° C.-104° C. To convert to its hydrochloride salt, the base was treated with one equivalent of 4N HCl in 50 mL absolute ethanol. The solution was concentrated in vacuo, redissolved in absolute ethanol, and concentrated in vacuo. Then the hydrochloride was recrystallized from absolute ethyl alcohol with little ethyl acetate, giving white crystals, m.p. 270° C.-271° C. (dec.).

Workup

  1. temperatureThe mixture was heated to 55° C.-60° C.
  2. waitUsually between 20 minutes to 5 hours were required for completion
  3. filtrationThe excess zinc was filtered off
  4. concentrationthe solution concentrated in vacuo
  5. extractionThe product was extracted with tetrahydrofuran
  6. customThen the free base was chromatographed
  7. concentrationconcentrated in vacuo
  8. customdried in high vacuum

Sources & evidence

ORD record
ord-174a86a6cc4a4588b7a14457662c3127
Source dataset
uspto-grants-1996_01
Patent number
US05486512

Reaction notes

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