Sodium Carbonate → 2-[1,1'-biphenyl]-4-yl-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine

HRID 861117Notes

Reaction equation

HRID 861117 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:21]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH:28][CH2:29][CH2:30][CH2:31][CH3:32])[N:23]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([NH:16][CH2:17][CH2:18][CH2:19][CH3:20])[N:10]3[N:9]=2)=[CH:4][CH:3]=1.[C:33]1(B(O)O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.CCOCC.O>[C:2]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:7]=[CH:6][C:5]([C:8]2[C:21]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH:28][CH2:29][CH2:30][CH2:31][CH3:32])[N:23]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([NH:16][CH2:17][CH2:18][CH2:19][CH3:20])[N:10]3[N:9]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 102068202-(4-Bromophenyl)-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine

Product 1

HCID 101634712-[1,1'-biphenyl]-4-yl-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amineYield 73%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(4-Bromophenyl)-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]pyrazolo-[1,5-a]pyridin-7-amine (52 mg, 0.11 mmol) in tetrahydrofuran was added phenylboronic acid (26 mg, 0.21 mmol), sodium carbonate (0.21 mL, 2 M aqueous, 0.42 mmol), and dichlorobistriphenylphosphine palladium (II) (7.5 mg, 0.01 mmol). The mixture was heated at reflux for 3.5 hours. The resultant solution was cooled to room temperature and diluted with ether and water was added. The organic layer was washed with brine. The aqueous layer was extracted with ether and the combined organics dried over magnesium sulfate. Filtration and concentration followed by flash chromatography provided 2-[1,1′-biphenyl]-4-yl-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine (37 mg, 73%) as a yellow solid. 1H NMR (CDCl3): δ 8.05 (d, 1 H), 7.83–7.69 (m, 7 H), 7.51 (m, 2 H), 7.43–7.33 (m, 2 H), 6.44 (d, 1 H), 6.12 (t, 1 H), 6.05 (d, 1 H), 5.16 (broad, 1 H), 3.52 (m, 2 H), 3.42 (m, 2 H), 1.84–1.43 (m, 8 H), 1.05–0.99 (m, 6 H); MS m/z 491 (M+1).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3.5 hours
  3. additionwas added
  4. washThe organic layer was washed with brine
  5. extractionThe aqueous layer was extracted with ether
  6. dry with materialthe combined organics dried over magnesium sulfate
  7. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-afd76683cf734f38b30a04176d30cac2
Source dataset
uspto-grants-2006_12
Patent number
US07153855B2

Reaction notes

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