Dimethylamine → 9-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-8-(4((dimethylamino)methyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3 (7H)-one

HRID 1467546Notes

Reaction equation

HRID 1467546 reaction equation
[CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][N:9]([C:12]([C:14]3[CH:19]=[CH:18][C:17]([CH:20]4[C:25]5=[N:26][NH:27][C:28](=[O:33])[C:29]6[CH:30]=[CH:31][CH:32]=[C:23]([C:24]=65)[NH:22][CH:21]4[C:34]4[CH:41]=[CH:40][C:37]([CH:38]=O)=[CH:36][CH:35]=4)=[CH:16][CH:15]=3)=[O:13])[CH2:8][CH2:7]2)=[O:5])[CH2:3][CH2:2]1.[CH3:42][NH:43][CH3:44].[BH4-].[Na+]>CO>[CH:1]1([C:4]([N:6]2[CH2:7][CH2:8][N:9]([C:12]([C:14]3[CH:19]=[CH:18][C:17]([CH:20]4[C:25]5=[N:26][NH:27][C:28](=[O:33])[C:29]6[CH:30]=[CH:31][CH:32]=[C:23]([C:24]=65)[NH:22][CH:21]4[C:34]4[CH:41]=[CH:40][C:37]([CH2:38][N:43]([CH3:44])[CH3:42])=[CH:36][CH:35]=4)=[CH:16][CH:15]=3)=[O:13])[CH2:10][CH2:11]2)=[O:5])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 674DimethylamineHCID 4311764Sodium borohydrideHCID 1363746694-(9-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-3-oxo-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde

Product 1

HCID 1360568549-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-8-(4((dimethylamino)methyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3 (7H)-oneYield 5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 4-(9-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-3-oxo-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde (80 mg, 0.15 mmol) and 27% dimethylamine solution (62 mg, 0.44 mmol) in methanol (10 mL) was stirred at room temperature for 40 min. Then the mixture was cooled to 0° C. Sodium borohydride (8.3 mg, 0.22 mmol) was added. After the addition, the mixture was stirred at this temperature for 2 hr. Methanol 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. The crude product was purified by prep-HPLC to give 9-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-8-(4((dimethylamino)methyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (4.2 mg, yield 5%) as a light yellow solid. 1H-NMR (400 MHz, CD3OD) δ (ppm): 0.73-0.79 (m, 4H), 1.84 (m, 1H), 2.69 (s, 6H), 3.47-3.72 (m, 8H), 4.14 (s, 2H), 4.31-4.33 (d, J=8.0 Hz, 1H), 7.12-7.35 (m, 9H), 7.47-7.58 (m, 2H); LC-MS (ESI) m/z: 577 (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. washThe residue was washed with ethyl acetate/methanol (10/1)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. customto give the crude product
  9. customThe crude product was purified by prep-HPLC

Sources & evidence

ORD record
ord-d583d7df4e6c41b087223067689e5a56
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Reaction notes

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