Diisopropylethylamine → 4-{[3-(Piperazine-1-carbonyl)phenyl]methyl}phthalazin-1(2H)-one

HRID 1402980Notes

Reaction equation

HRID 1402980 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][C:13]2[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=2)[C:16]([OH:18])=O)=[N:4][NH:3]1.[N:22]1(C(OC(C)(C)C)=O)[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>Cl.C(O)C.O.CC(N(C)C)=O>[N:22]1([C:16]([C:15]2[CH:14]=[C:13]([CH:21]=[CH:20][CH:19]=2)[CH2:12][C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:2](=[O:1])[NH:3][N:4]=2)=[O:18])[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 251319063-((4-Oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid

Product 1

HCID 251326124-{[3-(Piperazine-1-carbonyl)phenyl]methyl}phthalazin-1(2H)-oneYield 77%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

3-(4-Oxo-3,4-dihydrophthalazin-1-ylmethyl)benzoic acid (A)(5.0 g, 0.17 mol), tert-butyl 1-piperazinecarboxylate (3.9 g, 0.21 mol), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) (8.6 g, 0.22 mol) and N,N,-diisopropylethylamine (6.7 ml, 0.38 mol) were added to dimethylacetamide (40 ml) and stirred for 18 hours. Water (100 ml) was added and the reaction mixture was heated to 100° C. for 1 hour. The suspension was cooled to room temperature, filtered and dried to yield a white solid. The solid was dissolved in a solution of 6M HCl and ethanol (2:1, 50 ml) and stirred for 1 hour. The reaction was concentrated, basified with ammonia to pH 9, and the product was extracted into dichloromethane (2×50 ml). The combined organic layers were washed with water (2×50 ml), dried over MgSO4, and evaporated in vacuo to yield 4-[3-(piperazine-1-carbonyl)benzyl]-2H-phthalazin-1-one (1) as a yellow crystalline solid (4.0 g, 77%); m/z [M+1]+ 349 (97% purity), δH 2.6-3.8 (8H, m), 4.4 (2H, s), 7.2-7.5 (4H, m), 7.7-8.0 (3H, m), 8.2-8.3 (1H, m), 12.6 (1H, s)

Workup

  1. temperatureThe suspension was cooled to room temperature
  2. filtrationfiltered
  3. customdried
  4. customto yield a white solid
  5. stirringstirred for 1 hour
  6. concentrationThe reaction was concentrated
  7. extractionthe product was extracted into dichloromethane (2×50 ml)
  8. washThe combined organic layers were washed with water (2×50 ml)
  9. dry with materialdried over MgSO4
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-3f25ae1fd9b040ddaafbec13666228d4
Source dataset
uspto-grants-2014_12
Patent number
US08912187B2

Reaction notes

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