Cyclopropylamine → HCID 57956104, compound

HRID 2428093Notes

Reaction equation

HRID 2428093 reaction equation
[Cl:1][C:2]1[C:3]([CH:13]=O)=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][O:11][CH3:12])=[N:6][CH:7]=1.[CH:15]1([NH2:18])[CH2:17][CH2:16]1.[BH4-].[Na+]>CO>[Cl:1][C:2]1[C:3]([CH2:13][NH:18][CH:15]2[CH2:17][CH2:16]2)=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][O:11][CH3:12])=[N:6][CH:7]=1.[Cl:1][C:2]1[C:3]([CH:13]=[N:18][CH:15]2[CH2:17][CH2:16]2)=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][O:11][CH3:12])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 69828CyclopropylamineHCID 4311764Sodium borohydrideHCID 714237335-Chloro-2-(3-methoxypropyl)pyridine-4-carbaldehyde

Product 2

HCID 57956104HCID 57956104, compoundHCID 66761633HCID 66761633, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 5-chloro-2-(3-methoxy-propyl)-pyridine-4-carbaldehyde (21.0 g, 98.2 mmol) and cyclopropylamine (13.8 mL, 196 mmol) in MeOH (450 mL) was stirred at rt overnight. NaBH4 (4.83 g, 128 mmol) was added at 0° C., and the mixture was stirred at rt overnight. Ice was added, and the mixture was concentrated under reduced pressure. The crude product was dissolved in EtOAc, and this mixture was washed with aq. 1M NaOH. The aq. layer was extracted back with EtOAc. The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 1:5→1:4→1:3→1:1→3:1→EtOAc) yielded the title compound (11.8 g) and [5-chloro-2-(3-methoxy-propyl)-pyridin-4-ylmethylene]-cyclopropyl-amine (10.7 g). This unreacted imine was dissolved in MeOH (20 mL), and this sol. was cooled to 0° C. NaBH4 (3.20 g, 84.6 mmol) was added, and the mixture was stirred at rt overnight. NaBH4 (3.20 g, 84.6 mmol) was added again, and the mixture was stirred for 3 days. Ice was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The crude product was dissolved in EtOAc and the resulting mixture was washed with aq. 1M NaOH. The aq. phase was extracted back with EtOAc. The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 1:3→1:2→1:1→EtOAc) yielded the title compound (9.40 g). The fractions of the title compounds were mixed together (21.2 g, 85%). LC-MS: tR=0.55 min; ES+: 296.16.

Workup

  1. stirringthe mixture was stirred at rt overnight
  2. additionIce was added
  3. concentrationthe mixture was concentrated under reduced pressure
  4. dissolutionThe crude product was dissolved in EtOAc
  5. washthis mixture was washed with aq. 1M NaOH
  6. extractionThe aq. layer was extracted back with EtOAc
  7. dry with materialextracts were dried over MgSO4
  8. filtrationfiltered
  9. customthe solvents were removed under reduced pressure
  10. customPurification of the crude by FC (EtOAc/heptane 1:5→1:4→1:3→1:1→3:1→EtOAc)

Sources & evidence

ORD record
ord-e3de4acc447e41698f6debf9247265ec
Source dataset
uspto-grants-2011_06
Patent number
US07968720B2

Reaction notes

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