Acetic Acid → HCID 136186312, compound

HRID 1968109Notes

Reaction equation

HRID 1968109 reaction equation
[O:1]=[C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]3[NH:12][CH:13]([C:21]4[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=4)[CH:14]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[C:5]([C:6]=23)=[N:4][NH:3]1.[C:29](O)(=O)[CH3:30].[NH:33]1C[CH2:35][CH2:34]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CO>[C:15]1([CH:14]2[C:5]3=[N:4][NH:3][C:2](=[O:1])[C:11]4[CH:10]=[CH:9][CH:8]=[C:7]([C:6]=43)[NH:12][CH:13]2[C:21]2[CH:28]=[CH:27][C:24]([CH2:25][N:33]3[CH2:30][CH2:29][CH2:35][CH2:34]3)=[CH:23][CH:22]=2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 10422AzetidineHCID 5049666Sodium triacetoxyborohydrideHCID 136344752HCID 136344752, compound

Product 1

HCID 136186312HCID 136186312, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-(3-oxo-9-phenyl-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde (150 mg, 0.41 mmol) in dry dichloromethane (20 mL) and MeOH (2 mL) was added acetic acid (120 mg) followed by azetidine (70 mg, 1.23 mmol). After the addition, the mixture was stirred at room temperature overnight. Then sodium triacetoxyborohydride (131 mg, 0.62 mmol) was added at 0° C. After the addition, the mixture was stirred at this temperature for 5 hr. DCM was removed under reduced pressure. The residue was washed with ethyl acetate/methanol (10/1) and filtered. The filtrate was concentrated to give the crude product, which was purified by column chromatography (silica gel, dichloromethane/methanol=100:1 to 15:1) to give the title compound (84 mg, yield 51%) as yellow solid. LC-MS (ESI) m/z: 409 (M+1)+. 1H-NMR (400 MHz, CD3OD) δ (ppm): 2.38-2.43 (m, 2H), 3.98 (t, J=8 Hz, 4H), 4.20 (s, 2H), 4.27 (d, J=8 Hz, 1H), 4.77 (d, J=8 Hz, 1H), 7.03-7.05 (m, 2H), 7.10-7.17 (m, 4H), 7.27-7.35 (m, 4H), 7.50-7.52 (m, 1H), 7.57-7.62 (m, 1H).

Workup

  1. additionAfter the addition
  2. additionAfter the addition
  3. stirringthe mixture was stirred at this temperature for 5 hr
  4. customDCM was removed under reduced pressure
  5. washThe residue was washed with ethyl acetate/methanol (10/1)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. customto give the crude product, which
  9. customwas purified by column chromatography (silica gel, dichloromethane/methanol=100:1 to 15:1)

Sources & evidence

ORD record
ord-9190de29faab416db9fa7c6650bc633a
Source dataset
uspto-grants-2013_04
Patent number
US08420650B2

Reaction notes

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