1,1'-Carbonyldiimidazole → HCID 86743817, compound

HRID 1165771Notes

Reaction equation

HRID 1165771 reaction equation
[CH:1]([C:4]1[C:13]([OH:14])=[C:12]([CH:15]([CH3:17])[CH3:16])[CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][C:8]([CH3:21])([C:18]([OH:20])=[O:19])[O:9]2)([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.O[C@@H:35]1[C@H:41]([C:42]2[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=2)[S:40][C:39]2[C:50]3[C:55]([CH:56]=[CH:57][C:38]=2[N:37]([CH2:58][CH2:59][N:60]([CH3:62])[CH3:61])[C:36]1=[O:63])=[CH:54][CH:53]=[CH:52][CH:51]=3>O1CCCC1.CN(C)C1C=CN=CC=1>[OH:14][C:13]1[C:12]([CH:15]([CH3:16])[CH3:17])=[CH:11][C:10]2[O:9][C:8]([C:18]([O:20][CH:35]3[CH:41]([C:42]4[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=4)[S:40][C:39]4[C:50]5[C:55]([CH:56]=[CH:57][C:38]=4[N:37]([CH2:58][CH2:59][N:60]([CH3:62])[CH3:61])[C:36]3=[O:63])=[CH:54][CH:53]=[CH:52][CH:51]=5)=[O:19])([CH3:21])[CH2:7][CH2:6][C:5]=2[C:4]=1[CH:1]([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 13823438HCID 13823438, compoundHCID 19860949HCID 19860949, compound

Product 1

HCID 86743817HCID 86743817, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1.4 g (0.0048 mol) of (±)-5,7-diisopropyl-6-hydroxy-2-methylchroman-2-carboxylic acid in 25 ml dry tetrahydrofuran was added 0.09 g (0.0055 mol) of 1,1'-carbonyldiimidazol. After stirring at room temperature for 30 minutes, 2.0 g (0.0047 mol) (±)-cis-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-5-[2-(dimethylamino)ethyl]naphtho[1,2-b][1,4]thiazepin-4(5H)-one and 20 mg of 4-dimethylaminopyridine were added. The reaction mixture was stirred at room temperature for 17 hours, concentrated to dryness and the residue was partitioned between ethyl acetate and dilute ammonium hydroxide. The combined ethyl acetate solutions were washed with brine, dried (MgSO4) and the solvent was removed under reduced pressure. The residue was dissolved in acetonitrile and chromatographed on 70 g silica gel. The column was eluted with 75 ml portions of acetonitrile. Fractions 5-8 were combined and the solvent removed to give 1.3 g (40%) of isomer "A" as an amorphous solid, [α]D25 -74.31° (C 1.03, MeOH).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 17 hours
  2. concentrationconcentrated to dryness
  3. customthe residue was partitioned between ethyl acetate and dilute ammonium hydroxide
  4. washThe combined ethyl acetate solutions were washed with brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent was removed under reduced pressure
  7. dissolutionThe residue was dissolved in acetonitrile
  8. customchromatographed on 70 g silica gel
  9. washThe column was eluted with 75 ml portions of acetonitrile
  10. customthe solvent removed
  11. customto give 1.3 g (40%) of isomer "A" as an amorphous solid, [α]D25 -74.31° (C 1.03, MeOH)

Sources & evidence

ORD record
ord-2645f8af8fbb487f9e1105715c964e1b
Source dataset
uspto-grants-1990_03
Patent number
US04912102

Reaction notes

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