Dichloromethane → HCID 24954654, compound

HRID 1367342Notes

Reaction equation

HRID 1367342 reaction equation
ClCCl.Cl[C:5]1[N:6]=[C:7]([NH:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[S:8][C:9]=1[CH2:10][C:11]1[C:19]2[C:14](=[N:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1.[CH2:29]([Mg]Br)[CH3:30].O1CCCC1>C1(C)C=CC=CC=1.CCOCC.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:29]([C:5]1[N:6]=[C:7]([NH:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[S:8][C:9]=1[CH2:10][C:11]1[C:19]2[C:14](=[N:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)[CH3:30]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 8028TetrahydrofuranHCID 24954653HCID 24954653, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 24954654HCID 24954654, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent2×HCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

Into a round bottom flask, under an atmosphere of nitrogen, [1,1′-bis(diphenyl phosphino) ferrocene] dichloro palladium (II), complex with dichloromethane (1:1), was placed with toluene (15 mL, 140 mmol). [4-Chloro-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-thiazol-2-yl]-(4-fluoro-benzyl)-amine (P-0156, 145 mg, 0.4 mmol) was added in 5 ml of toluene at room temperature. The mixture was stirred for 10 minutes. To the stirring reaction, a solution of 3.13 M ethyl magnesium bromide in ether (1.86 mL) was added dropwise at room temperature. The opaque solution was heated to 60° C. Tetrahydrofuran (10 mL) was added to the warm solution. The mixture was heated to reflux for an additional two hours. After cooling to 0° C., the reaction was quenched with a solution of citric acid at pH 4-5 in ice-water and stirred to room temperature. The mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate and brine. The organic layer was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. Purification with flash chromatography, eluting with a gradient of ethyl acetate:hexanes (20:100), gave a yellow solid that was further washed with ethyl acetate to give P-0162 (15 mg,10%) as an off-white solid. MS (ESI) [M+H+]+=367.2.

Workup

  1. customTo the stirring reaction
  2. temperatureThe mixture was heated
  3. temperatureto reflux for an additional two hours
  4. temperatureAfter cooling to 0° C.
  5. customthe reaction was quenched with a solution of citric acid at pH 4-5 in ice-water
  6. stirringstirred to room temperature
  7. additionThe mixture was diluted with ethyl acetate
  8. washwashed with saturated sodium bicarbonate and brine
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  10. customthe solvent was removed under reduced pressure
  11. customPurification with flash chromatography
  12. washeluting with a gradient of ethyl acetate:hexanes (20:100)
  13. customgave a yellow solid
  14. washthat was further washed with ethyl acetate
  15. customto give P-0162 (15 mg,10%) as an off-white solid

Sources & evidence

ORD record
ord-ecae90d9465941d594b2840dfe4b0ec7
Source dataset
uspto-grants-2011_02
Patent number
US07893075B2

Reaction notes

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