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Triphenylphosphine → 1-(2-Chloro-3,6-difluorobenzyl)-7-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1,4-dihydro-2H-pyrido[2,3-b]pyrazin-3-one

HRID 2074820
Notes
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Reaction equation

HRID 2074820 reaction equation
Br[C:2]1[CH:22]=[N:21][C:5]2[NH:6][C:7](=[O:20])[CH2:8][N:9]([CH2:10][C:11]3[C:16]([F:17])=[CH:15][CH:14]=[C:13]([F:18])[C:12]=3[Cl:19])[C:4]=2[CH:3]=1.[CH3:23][N:24]1[CH2:29][CH2:28][N:27]([C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][N:31]=2)[CH2:26][CH2:25]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(O)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:19][C:12]1[C:13]([F:18])=[CH:14][CH:15]=[C:16]([F:17])[C:11]=1[CH2:10][N:9]1[CH2:8][C:7](=[O:20])[NH:6][C:5]2[N:21]=[CH:22][C:2]([C:33]3[CH:32]=[N:31][C:30]([N:27]4[CH2:26][CH2:25][N:24]([CH3:23])[CH2:29][CH2:28]4)=[CH:35][CH:34]=3)=[CH:3][C:4]1=2
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 27696181-Methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazineHCID 578858627-Bromo-1-(2-chloro-3,6-difluorobenzyl)-1,4-dihydro-2H-pyrido[2,3-b]pyrazin-3-one

Product 1

HCID 578860121-(2-Chloro-3,6-difluorobenzyl)-7-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1,4-dihydro-2H-pyrido[2,3-b]pyrazin-3-oneYield 29%

Reagents, catalysts & solvents

2
HCID 167845palladium(II) acetateCatalystHCID 10311-PropanolSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 7-bromo-1-(2-chloro-3,6-difluorobenzyl)-1,4-dihydro-2H-pyrido[2,3-b]pyrazin-3-one (42 mg, 0.11 mmol), 1-methyl-4-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-2-yl]piperazine (40 mg, 0.13 mmol), palladium (II) acetate (4 mg) and triphenylphosphine (14 mg) in n-propanol (1.0 mL) was degassed with argon while adding a 1.26 M aqueous solution of Na2CO3 (0.12 mL) followed by water (0.38 mL). This mixture was heated in a microwave for 10 minutes at 130° C., cooled to room temperature and extracted into CH2Cl2. The organic phase was passed through a plug of Na2SO4, absorbed onto florisil and evaporated to dryness. This material was purified by silica gel chromatography by eluting with increasing amounts of 5% NH4OH/methanol in dichloromethane. The isolated material was recrystallized from methanol to give the title compound (15.4 mg, 29%). m.p. 235-236° C. (dec); LCMS: m/z=485/487 (M+H+); 1H-NMR (CDCl3-d6, 400 MHz) δ 8.22 (d, J=2.4 Hz, 1H), 7.89 (d, J=2.4 Hz, 1H), 7.49-7.46 (m, 1H), 7.16 (s, 1H), 7.15-7.06 (m, 1H), 7.05-6.93 (m, 1H), 6.69 (d, J=8.8, 1H), 5.43, (s, 2H), 4.81 (s, 1H), 4.24 (s, 2H), 3.61-3.59 (m, 4H), 2.55-2.52 (m, 4H), 2.36 (s, 3H).

Workup

  1. customwas degassed with argon
  2. additionwhile adding a 1.26 M aqueous solution of Na2CO3 (0.12 mL)
  3. temperaturecooled to room temperature
  4. extractionextracted into CH2Cl2
  5. customabsorbed onto florisil
  6. customevaporated to dryness
  7. customThis material was purified by silica gel chromatography
  8. washby eluting with increasing amounts of 5% NH4OH/methanol in dichloromethane
  9. customThe isolated material was recrystallized from methanol

Sources & evidence

ORD record
ord-38c4f9bce0f14570bc5a9ee6da81103d
Source dataset
uspto-grants-2011_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07919502B2

Reaction notes

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