Diisopropanolamine → 6,11-dihydro-alpha-(1H-imidazol-2-yl)-11-[1-[2-[4-(2-quinolinylmethoxy)phenyl]ethyl]-4-piperidinylidene]-5H-imidazo[2,1-b][3]benzazepine-3-methanol

HRID 1264570Notes

Reaction equation

HRID 1264570 reaction equation
CC(O)CNCC(O)C.C(OC(OCC)[N:14]1[CH:18]=[CH:17][N:16]=[CH:15]1)C.[N:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][C:23]=1[CH2:32][O:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40][CH2:41][N:42]2[CH2:47][CH2:46][C:45](=[C:48]3[C:54]4[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=4[CH2:52][CH2:51][N:50]4[C:59]([CH:62]=[O:63])=[CH:60][N:61]=[C:49]34)[CH2:44][CH2:43]2)=[CH:36][CH:35]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.C(O)(=O)C>[NH:14]1[CH:18]=[CH:17][N:16]=[C:15]1[CH:62]([C:59]1[N:50]2[C:49]([C:48](=[C:45]3[CH2:44][CH2:43][N:42]([CH2:41][CH2:40][C:37]4[CH:38]=[CH:39][C:34]([O:33][CH2:32][C:23]5[CH:24]=[CH:25][C:26]6[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=6)[N:22]=5)=[CH:35][CH:36]=4)[CH2:47][CH2:46]3)[C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=3[CH2:52][CH2:51]2)=[N:61][CH:60]=1)[OH:63]

Participants

7

Reactant 4

HCID 8086DiisopropanolamineHCID 11430Potassium CarbonateHCID 38495351-(diethoxymethyl)-1H-imidazoleHCID 99156646,11-dihydro-11-[1-[2-[4-(2-quinolinylmethoxy)phenyl]ethyl]-4-piperidinylidene]-5H-imidazo[2,1-b][3]benzazepine-3-carboxaldehyde

Product 1

HCID 186125076,11-dihydro-alpha-(1H-imidazol-2-yl)-11-[1-[2-[4-(2-quinolinylmethoxy)phenyl]ethyl]-4-piperidinylidene]-5H-imidazo[2,1-b][3]benzazepine-3-methanolYield 98.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A mixture of diisopropanolamine (1.13 g) in TBF was stirred under nitrogen at −78° C. N-Butillithium (2.5 M in hexanes, 4.3 ml) was added portionwise at −70° C. and the mixture was stirred for 15 minutes. 1-(Diethoxymethyl)-1H-imidazole (1.81 g) dissolved in THF was added dropwise at −70° C. and the mixture was stirred at −70° C. for 1 hour. Compound 4 (5.54 g) dissolved in THF was added dropwise at −70° C. and the mixture was stirred at −70° C. for 1 hour. The mixture was brought till room temperature and it was stirred at room temperature overnight. Acetic acid (5 ml) was added and the mixture was stirred at room temperature for 20 minutes. K2CO3 (5 g) was added and the mixture was evaporated. The residue was taken up in water and DCM and the layers were separated. The aqueous layer was extracted with DCM. The combined organic layers were dried, filtered off and the solvent was evaporated, yielding 6.1 g (97%) of 6,11-dihydro-α-(1H-imidazol-2-yl)-11-[1-[2-[4-(2-quinolinylmethoxy)phenyl]ethyl]-4-piperidinylidene]-5H-imidazo[2,1-b][3]benzazepine-3-methanol (compound 46).

Workup

  1. stirringthe mixture was stirred for 15 minutes
  2. additionwas added dropwise at −70° C.
  3. stirringthe mixture was stirred at −70° C. for 1 hour
  4. additionwas added dropwise at −70° C.
  5. stirringthe mixture was stirred at −70° C. for 1 hour
  6. customwas brought till room temperature
  7. stirringit was stirred at room temperature overnight
  8. stirringthe mixture was stirred at room temperature for 20 minutes
  9. customthe mixture was evaporated
  10. customDCM and the layers were separated
  11. extractionThe aqueous layer was extracted with DCM
  12. customThe combined organic layers were dried
  13. filtrationfiltered off
  14. customthe solvent was evaporated

Sources & evidence

ORD record
ord-c597268c0cbc47c881e2892b2068a202
Source dataset
uspto-grants-2003_04
Patent number
US06544979B1

Reaction notes

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