Cyclopropylamine → HCID 136130841, compound

HRID 1968007Notes

Reaction equation

HRID 1968007 reaction equation
[O:1]=[C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]3[NH:12][CH:13]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:14]([C:15]4[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=4)[CH:18]=O)[C:5]([C:6]=23)=[N:4][NH:3]1.[CH:29]1([NH2:32])[CH2:31][CH2:30]1.[BH4-].[Na+]>CO>[CH:29]1([NH:32][CH2:18][C:17]2[CH:16]=[C:15]([CH:14]3[C:5]4=[N:4][NH:3][C:2](=[O:1])[C:11]5[CH:10]=[CH:9][CH:8]=[C:7]([C:6]=54)[NH:12][CH:13]3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:22]=[CH:21][CH:20]=2)[CH2:31][CH2:30]1

Participants

5

Reactant 3

HCID 69828CyclopropylamineHCID 4311764Sodium borohydrideHCID 136344723HCID 136344723, compound

Product 1

HCID 136130841HCID 136130841, compoundYield 19.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 3-(3-oxo-8-phenyl-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-9-yl)benzaldehyde (70 mg, 0.19 mmol) and cyclopropanamine (32.55 mg, 0.57 mmol) in anhydrous methanol (10 mL) was stirred at room temperature for 1.5 h. Then the mixture was cooled to 0° C., sodium borohydride (10.82 mg, 0.286 mmol) was added portion-wise. After the addition, the mixture was stirred at this temperature for 2 hr. Methanol was removed under reduced pressure. The residue was dissolved in ethyl acetate (50 mL), extracted with 1N hydrochloric acid (20 mL), the aqueous layer was separated. The organic layer was washed with 1N hydrochloric acid (20 mL). The combined aqueous layers were adjusted to pH=9 with potassium carbonate, extracted with ethyl acetate (25 mL×4). The combined organic layers were dried over anhydrous sodium sulfate, and concentrated to give 9-(3-((cyclopropylamino)methyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (15 mg, yield 19%) as a light yellow solid. 1H-NMR (400 MHz, CD3OD) δ (ppm): 0.19-0.29 (m, 4H), 1.74-1.80 (m, 1H), 3.55 (s, 2H), 4.16-4.19 (d, J=8.8 Hz, 1H), 4.60-4.62 (d, J=8.8 Hz, 1H), 6.88-6.90 (d, J=7.6 Hz, 1H), 6.95 (s, 1H), 7.01-7.10 (m, 6H), 7.13-7.15 (m, 2H), 7.42-7.44 (d, J=7.6 Hz, 1H), 7.48-7.75 (t, J=8.0 Hz, 1H); LC-MS (ESI) m/z: 408 (M+1)+.

Workup

  1. temperatureThen the mixture was cooled to 0° C.
  2. additionAfter the addition
  3. stirringthe mixture was stirred at this temperature for 2 hr
  4. customMethanol was removed under reduced pressure
  5. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  6. extractionextracted with 1N hydrochloric acid (20 mL)
  7. customthe aqueous layer was separated
  8. washThe organic layer was washed with 1N hydrochloric acid (20 mL)
  9. extractionextracted with ethyl acetate (25 mL×4)
  10. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-efb6633f7085483a98831014bce6196b
Source dataset
uspto-grants-2013_04
Patent number
US08420650B2

Reaction notes

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