Hydrochloric Acid → HCID 18638175, compound

HRID 1165770Notes

Reaction equation

HRID 1165770 reaction equation
[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.O[C@@H:23]1[C@H:29]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)[S:28][C:27]2[C:38]3[C:43]([CH:44]=[CH:45][C:26]=2[N:25]([CH2:46][CH2:47][N:48]([CH3:50])[CH3:49])[C:24]1=[O:51])=[CH:42][CH:41]=[CH:40][CH:39]=3.[ClH:52]>O1CCCC1.CC(C)=O>[ClH:52].[ClH:52].[CH3:37][O:36][C:33]1[CH:34]=[CH:35][C:30]([C@@H:29]2[S:28][C:27]3[C:38]4[C:43]([CH:44]=[CH:45][C:26]=3[N:25]([CH2:46][CH2:47][N:48]([CH3:50])[CH3:49])[C:24](=[O:51])[C@@H:23]2[O:8][C:1]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)=[O:9])=[CH:42][CH:41]=[CH:40][CH:39]=4)=[CH:31][CH:32]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 938Nicotinic AcidHCID 682631,1'-CarbonyldiimidazoleHCID 13823438HCID 13823438, compound

Product 1

HCID 18638175HCID 18638175, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 0.5 g (0.004 mol) of nicotinic acid and 0.7 g (0.004 mol) of 1,1'-carbonyldiimidazole in 20 ml of dry tetrahydrofuran was stirred at room temperature for 1 hour. To the solution was added 1.3 g (0.003 mol) of (±)-cis-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-5-(2-(dimethylamino)ethyl]naphtho[1,2-b][1,4]thiazepin-4(5H)-one and the reaction mixture was stirred at room temperature for 17 hours. After concentrating to dryness the residue was partitioned between ethyl acetate and dilute ammonium hydroxide. The ethyl acetate solutions were washed with brine and dried (MgSO4). Removal of the solvent at reduced pressure gave 2.2 g of crude base which was dissolved in acetone and acidified with hydrogen chloride (anhydrous). The resulting crystals were separated to afford 1.9 g (99%) of (±)-cis-2,3-dihydro-2-(4-methoxyphenyl)-5-[2-(dimethylamino)ethyl]-3-[(3-pyridinylcarbonyl)oxy]naphtho[1,2-b][1,4]thiazepin-4 (4H)-one dihydrochloride (4:5) hydrate, mp 178°-179°.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 17 hours
  2. concentrationAfter concentrating to dryness the residue
  3. customwas partitioned between ethyl acetate and dilute ammonium hydroxide
  4. washThe ethyl acetate solutions were washed with brine
  5. dry with materialdried (MgSO4)
  6. customRemoval of the solvent at reduced pressure
  7. customgave 2.2 g of crude base which
  8. customThe resulting crystals were separated

Sources & evidence

ORD record
ord-24afb79455f04b5f8e0e7e9ab8d624da
Source dataset
uspto-grants-1990_03
Patent number
US04912102

Reaction notes

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