Methanol → HCID 87222526, compound

HRID 712307Notes

Reaction equation

HRID 712307 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[S:8][C:9]2[C:15]([CH2:16][NH:17][CH3:18])=[CH:14][C:13]([C:19]3[CH:20]=[N:21][C:22]([N:25]4[CH2:30][CH2:29][C:28]([CH3:36])([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:27][CH2:26]4)=[N:23][CH:24]=3)=[CH:12][C:10]=2[N:11]=1)=[O:5])[CH3:2].CCN(C(C)C)C(C)C.Cl[C:47]1[N:52]=[CH:51][CH:50]=[CH:49][N:48]=1.CO>C(O)(C)C.C(Cl)Cl>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[S:8][C:9]2[C:15]([CH2:16][N:17]([CH3:18])[C:47]3[N:52]=[CH:51][CH:50]=[CH:49][N:48]=3)=[CH:14][C:13]([C:19]3[CH:20]=[N:21][C:22]([N:25]4[CH2:30][CH2:29][C:28]([CH3:36])([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:27][CH2:26]4)=[N:23][CH:24]=3)=[CH:12][C:10]=2[N:11]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 744042-ChloropyrimidineHCID 81531Diisopropylethylamine2×HCID 86664020HCID 86664020, compound

Product 1

HCID 87222526HCID 87222526, compoundYield 27.1%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Ethyl 1-[5-[2-(ethylcarbamoylamino)-7-(methylaminomethyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (130 mg, 0.25 mmol), N,N′-diisopropylethylamine (3.69 mmol, 477 mg, 324 ul) and 2-chloropyrimidine (1.75 mmol, 200 mg) were combined in isopropanol (2 mL) in a microwave tube equipped with a stirrer. The tube was purged with N2, sealed and irradiated to 110° C. for 1 hr in a CEM explorer microwave with stirring however LCMS indicated only starting material was present and the reaction was diluted with isopropanol (4 mL) and N,N′-diisopropylethylamine (4.19 mmol, 540 mg, 400 ul), then purged with N2, sealed then irradiated to 110° C. for 1 hr in the CEM explorer with stirring. LCMS indicated conversion to the desired product along with the corresponding isopropylester and starting material. The reaction was allowed to cool, the solvents removed under reduced pressure and the resulting residue partitioned between EtOAc and water and the layers separated. The aqueous portion was extracted with EtOAc and the combined organic portions dried (MgSO4) and concentrated to afford the crude product (160 mg). This material was purified by flash silica chromatography eluting with 0 to 50% EtOAc in petroleum-ether then 0 to 10% MeOH in DCM to afford the target material (40 mg, 27% yield).

Workup

  1. customequipped with a stirrer
  2. customThe tube was purged with N2
  3. customsealed
  4. customirradiated to 110° C. for 1 hr in a CEM explorer microwave
  5. custompurged with N2
  6. customsealed
  7. customthen irradiated to 110° C. for 1 hr in the CEM explorer
  8. stirringwith stirring
  9. temperatureto cool
  10. customthe solvents removed under reduced pressure
  11. customthe resulting residue partitioned between EtOAc and water
  12. customthe layers separated
  13. extractionThe aqueous portion was extracted with EtOAc
  14. dry with materialthe combined organic portions dried (MgSO4)
  15. concentrationconcentrated
  16. customto afford the crude product (160 mg)
  17. customThis material was purified by flash silica chromatography
  18. washeluting with 0 to 50% EtOAc in petroleum-ether

Sources & evidence

ORD record
ord-7aa88fbdc9074d4abb3a1d77f3fb1644
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

Loading…