Diisopropylamine → HCID 69279612, compound

HRID 968494Notes

Reaction equation

HRID 968494 reaction equation
C([Li])CCC.CC(NC(C)C)C.[CH3:13][N:14]1[C:22]2[C:17](=[N:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15]1.[C:23]1([CH2:29][N:30]2[CH2:36][CH2:35][CH2:34][C:33](=[O:37])[CH2:32][CH2:31]2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[NH4+].[Cl-]>C1COCC1.O>[CH3:13][N:14]1[C:22]2[C:17](=[N:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[C:15]1[C:33]1([OH:37])[CH2:34][CH2:35][CH2:36][N:30]([CH2:29][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:31][CH2:32]1

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 15143501-Benzyl-hexahydro-4H-azepin-4-oneHCID 122993501-Methyl-1H-imidazo[4,5-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 69279612HCID 69279612, compoundYield 34.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-70 °C

Procedure

n-Butyllithium (1.6M in hexanes, 0.164 mol) was added dropwise at −30° C. under N2 flow to a mixture of N-(1-methylethyl)-2-propanamine (0.164 mol) in THF (70 ml). The mixture was cooled to −70° C. A mixture of 1-methyl-1H-imidazo[4,5-b]pyridine (0.0751 mol) in THF (70 ml) was added dropwise. The mixture was stirred for 1 hour. A mixture of hexahydro-1-(phenylmethyl)-4H-azepin-4-one (0.0787 mol) in THF (60 ml) was added at −70° C. The mixture was stirred at −70° C. for 2 hours, brought to 0° C., poured out into water and NH4Cl and extracted with DCM and a small amount of methanol. The organic layer was separated, dried, filtered and evaporated to dryness. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 97/3/0.5). The desired fractions were collected and the solvent was evaporated, yielding 8.8 g of (±)-hexahydro-4-(1-methyl-1H-imidazo[4,5-b]pyridin-2-yl)-1-(phenylmethyl)-1H-azepin-4-ol (compound 152).

Workup

  1. additionwas added dropwise
  2. additionwas added at −70° C
  3. stirringThe mixture was stirred at −70° C. for 2 hours
  4. custombrought to 0° C.
  5. extractionextracted with DCM
  6. customThe organic layer was separated
  7. customdried
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 97/3/0.5)
  11. customThe desired fractions were collected
  12. customthe solvent was evaporated

Sources & evidence

ORD record
ord-3bb6af7eef8c46be9731437dcffb68c4
Source dataset
uspto-grants-2007_12
Patent number
US07304052B2

Reaction notes

Loading…