Dimethylamine → 1-(4-methoxyphenyl)-6-[4-(2-oxo-1-piperidinyl)phenyl]1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one

HRID 2222594Notes

Reaction equation

HRID 2222594 reaction equation
Br[C:2]1[C:10]2[CH2:9][CH2:8][N:7]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH2:22][CH2:21][CH2:20][CH2:19][C:18]4=[O:23])=[CH:13][CH:12]=3)[C:6](=[O:24])[C:5]=2[N:4]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[N:3]=1.CNC.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>C1(C)C=CC=CC=1.O1CCOCC1>[CH3:32][O:31][C:28]1[CH:27]=[CH:26][C:25]([N:4]2[C:5]3[C:6](=[O:24])[N:7]([C:11]4[CH:16]=[CH:15][C:14]([N:17]5[CH2:22][CH2:21][CH2:20][CH2:19][C:18]5=[O:23])=[CH:13][CH:12]=4)[CH2:8][CH2:9][C:10]=3[CH:2]=[N:3]2)=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 101175123-bromo-1-(4-methoxyphenyl)-6-[4-(2-oxo-1-piperidinyl)phenyl]1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-oneHCID 23676156Sodium t-butoxide

Product 1

HCID 102733951-(4-methoxyphenyl)-6-[4-(2-oxo-1-piperidinyl)phenyl]1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-oneYield 20%

Reagents, catalysts & solvents 1

HCID 21840791Dioxane tolueneSolvent

Conditions

Temperature
85 °C

Procedure

To 3-bromo-1-(4-methoxyphenyl)-6-[4-(2-oxo-1-piperidinyl)phenyl]1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one (Example 21) (0.15 g, 0.3 mmol), dimethylamine (2M THF, 1.5 mL, 3 mmol), sodium t-butoxide (88 mg, 0.9 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (7 mg), was added toluene/dioxane (1:1) (15 mL) and the mixture was degassed with N2. Pd2(dba)3 was added and the reaction was heated to 85° C. for 24 h. The reaction was cooled, diluted with ethyl acetate and filtered through Celite. Purification by HPLC and freeze-drying afforded 25 mg (18%) of the title compound; HRMS (M+Na)+ for C24H24NaN4O3 was 439.1726; 1H NMR (CDCl3) δ 7.59 (s, 1H), 7.47 (d,j=8.8 Hz, 2H), 7.36 (d,j=8.8 Hz, 2H), 7.26 (d,j=9.1 Hz, 2H), 6.92 (d,j=9.2 Hz, 2H), 4.10 (t,j=6.6 Hz, 2H), 3.60 (m, 2H), 3.81 (s, 3H), 3.03 (t,j=6.6 Hz, 2H), 2.57 (m, 2H), 1.94 (m, 4H) ppm.

Workup

  1. customthe mixture was degassed with N2
  2. additionPd2(dba)3 was added
  3. temperatureThe reaction was cooled
  4. additiondiluted with ethyl acetate
  5. filtrationfiltered through Celite
  6. customPurification by HPLC
  7. customfreeze-drying

Sources & evidence

ORD record
ord-b85988d4dd2f42b192de96a8358198e7
Source dataset
uspto-grants-2008_05
Patent number
US07371761B2

Reaction notes

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