Acetic Acid → HCID 136056881, compound

HRID 907857Notes

Reaction equation

HRID 907857 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(O)(=O)C.[N:33]1(C(OC(C)(C)C)=O)[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCl>[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:22]=[CH:23][C:24]([CH2:25][N:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)=[CH:27][CH:28]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 136344752HCID 136344752, compound

Product 1

HCID 136056881HCID 136056881, compoundYield 53.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(3-oxo-9-phenyl-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde (200 mg, 0.54 mmol) in dichloromethane (30 mL) was added acetic acid (196 mg, 3.24 mmol) and tert-butyl piperazine-1-carboxylate (304 mg, 1.63 mmol) at room temperature and stirred overnight. Then NaBH(OAc)3 (173 mg, 0.81 mmol) was added to the mixture at 0° C., stirred for one day. The reaction mixture was quenched with aqueous sodium bicarbonate, extracted with dichloromethane. The combined organic layer was washed by brine, dried over anhydrous sodium sulfate, concentrated to give the crude product which was purified by flash chromatography to obtain a solution. To the solution obtained (concentrated to about 50 mL) was added conc. HCl (10 mL) at room temperature and stirred overnight. The mixture was extracted with ethyl acetate for three times, the aqueous phase was concentrated to give 9-phenyl-8-(4-(piperazin-1-ylmethyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (127 mg, yield 46%). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 3.47 (br s, 7H), 3.60 (m, 1H), 4.32 (s, 2H), 4.38 (d, 1H), 4.83 (d, 1H), 5.41 (br s, 2H), 7.19 (m, 6H), 7.24 (m, 3H), 7.55 (m, 4H), 9.87 (br s, 2H), 12.20 (s, 1H); LC-MS (ESI) m/z: 438(M+1)+.

Workup

  1. stirringstirred for one day
  2. customThe reaction mixture was quenched with aqueous sodium bicarbonate
  3. extractionextracted with dichloromethane
  4. washThe combined organic layer was washed by brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customto give the crude product which
  8. customwas purified by flash chromatography
  9. customto obtain a solution
  10. customTo the solution obtained
  11. concentration(concentrated to about 50 mL)
  12. additionwas added conc. HCl (10 mL) at room temperature
  13. stirringstirred overnight
  14. extractionThe mixture was extracted with ethyl acetate for three times
  15. concentrationthe aqueous phase was concentrated

Sources & evidence

ORD record
ord-4fec5719fa4d4916b1b003a7be0366e5
Source dataset
uspto-grants-2011_09
Patent number
US08012976B2

Reaction notes

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