Ethyl Acetate → HCID 178513031, compound

HRID 75041Notes

Reaction equation

HRID 75041 reaction equation
[F:1][C:2]1[C:3]([NH:28][C@H:29]2[CH2:34][CH2:33][CH2:32][C@@H:31]([NH:35][C:36]([NH:38]C(=O)OC(C)(C)C)=[NH:37])[CH2:30]2)=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[N:10](S(C3C=CC(C)=CC=3)(=O)=O)[CH:9]=2)=[N:6][CH:7]=1.C[O-].[Na+].CCOC(C)=O.C([O-])(O)=O.[Na+]>C1COCC1>[F:1][C:2]1[C:3]([NH:28][C@H:29]2[CH2:34][CH2:33][CH2:32][C@@H:31]([NH:35][C:36]([NH2:38])=[NH:37])[CH2:30]2)=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][CH:9]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 10942334Sodium MethoxideHCID 178427348HCID 178427348, compound2×

Product 1

HCID 178513031HCID 178513031, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl N—[N-[(1R,3S)-3-[[5-fluoro-2-[5-fluoro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-4-yl]amino]cyclohexyl]carbamimidoyl]carbamate, 70c, (0.100 g, 0.156 mmol) in THF (20 mL) was added sodium methoxide (0.033 g, 0.156 mmol) at room temperature. After 1 minute, the reaction mixture was diluted into EtOAc and aqueous saturated NaHCO3 solution. The organic phase was dried over MgSO4, filtered and the solvent was removed under reduced pressure. The resulting residue was purified by silica gel chromatography to afford 95 mg of the desired product. To 10 ml MeOH solution of the product was added hydrochloride/IPA (0.031 mL of 5 M solution, 0.156 mmol). The reaction mixture was stirred at room temperature for 1 hour after which the solvent was removed under reduced pressure to afford the product, as hydrochloride salt: 1H NMR (300 MHz, MeOD) δ 8.63 (s, 1H), 8.40 (dd, J=9.1, 2.7 Hz, 1H), 8.36 (s, 1H), 8.32 (d, J=5.5 Hz, 1H), 4.46 (d, J=11.7 Hz, 1H), 3.78-3.53 (m, 1H), 2.41 (d, J=11.7 Hz, 1H), 2.28 (d, J=12.0 Hz, 1H), 2.18-1.98 (m, 2H), 1.69 (dd, J=23.6, 11.8 Hz, 2H), 1.56-1.28 (m, 2H); LCMS RT=1.45 (M+H) 387.06.

Workup

  1. dry with materialThe organic phase was dried over MgSO4
  2. filtrationfiltered
  3. customthe solvent was removed under reduced pressure
  4. customThe resulting residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-d8875959b47244c5ad3b6753cd82eae8
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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