Acetoacetic Acid → HCID 10123048, compound

HRID 861172Notes

Reaction equation

HRID 861172 reaction equation
[CH:1]1([NH:6][C:7]2[N:12]=[C:11]([C:13]3[C:14]([C:28]4[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=4)=[N:15][N:16]4[C:21]([NH:22][CH2:23][CH2:24][CH2:25][CH2:26][OH:27])=[CH:20][CH:19]=[CH:18][C:17]=34)[CH:10]=[CH:9][N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.N1C=NN=N1.C(N(C(C)C)[P:45](=[O:62])([O:54][CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)(C)C.CC(CC(O)=O)=O.S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)(O)[O-].[Na+]>ClCCl>[P:45]([O:27][CH2:26][CH2:25][CH2:24][CH2:23][NH:22][C:21]1[N:16]2[N:15]=[C:14]([C:28]3[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=3)[C:13]([C:11]3[CH:10]=[CH:9][N:8]=[C:7]([NH:6][CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)[N:12]=3)=[C:17]2[CH:18]=[CH:19][CH:20]=1)([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)([O:54][CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)=[O:62]

Participants

8

Reactant 6

HCID 96Acetoacetic AcidHCID 24477Sodium ThiosulfateHCID 516892Sodium BicarbonateHCID 10140204HCID 10140204, compoundHCID 11057523HCID 11057523, compound2×HCID 178418441HCID 178418441, compound

Product 1

HCID 10123048HCID 10123048, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a room temperature solution of 4-{[3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]amino}butan-1-ol (22 mg, 0.05 mmol) in dichloromethane (5 mL) was added 1-H-tetrazole (7 mg, 0.1 mmol) and dibenzyl N,N-diisopropylphosphoramidate (0.32 mL of a stock solution prepared from 0.2 mL of dibenzyl N,N-diisopropylphosphoramidate in 3.2 mL of dichloromethane). The resultant solution was stirred at room temperature for 1 hour and then cooled to 0° C. lodobenzene diacetate (16.5 mg, 0.05 mmol) was added and the mixture was stirred for 20 minutes. Saturated aqueous sodium thiosulfate and saturated aqueous sodium bicarbonate were added and the layers separated. The organic layer was washed with brine. The aqueous layer was extracted with dichloromethane and the combined organics were dried over sodium sulfate. Filtration and concentration followed by flash chromatography (1:4 hexanes-ethyl acetate) provided dibenzyl 4-{[3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]amino}butyl phosphate (18 mg, 53%). 1H NMR (CDCl3): δ 8.03 (d, 1 H), 7.81 (d, 1 H), 7.61 (d, 2 H), 7.38–7.32 (m, 11 H), 7.01 (d, 2 H), 6.36 (d, 1 H), 6.06 (m, 1 H), 5.98 (d, 1 H), 5.13–5.01 (m, 5 H), 4.40 (m, 1 H), 4.05 (m, 2 H), 3.91 (s, 3 H), 3.37 (m, 2 H), 2.16–1.54 (m, 12 H); MS m/z 733 (M+1).

Workup

  1. additionwas added
  2. customthe layers separated
  3. washThe organic layer was washed with brine
  4. extractionThe aqueous layer was extracted with dichloromethane
  5. dry with materialthe combined organics were dried over sodium sulfate
  6. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-e97c9f39f40344a7a5ae31f12bd3880d
Source dataset
uspto-grants-2006_12
Patent number
US07153855B2

Reaction notes

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