Cesium carbonate → HCID 178439566, compound

HRID 2168236Notes

Reaction equation

HRID 2168236 reaction equation
[CH3:1][CH:2]([C:4]1[C:12]2[C:11]([N:13]3[CH2:18][CH2:17][CH:16]([NH:19][C:20](=[O:27])[C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:15][CH2:14]3)=[N:10][CH:9]=[N:8][C:7]=2[N:6](S(C2C=CC=CC=2)(=O)=O)[CH:5]=1)[CH3:3].C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.CO>[CH3:3][CH:2]([C:4]1[C:12]2[C:7]([NH:8][CH:9]=[N:10][C:11]=2[N:13]2[CH2:14][CH2:15][CH:16]([NH:19][C:20](=[O:27])[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:17][CH2:18]2)=[N:6][CH:5]=1)[CH3:1]

Participants

5

Reactant 2

HCID 10796Cesium carbonateHCID 67988079HCID 67988079, compound

Product 1

HCID 178439566HCID 178439566, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-{1-[5-(1-methylethyl)-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-4-piperidinyl}benzamide D9 (140 mg) in THF (2 mL) and MeOH (1 mL) was added cesium carbonate (272 mg, 0.834 mmol) and the mixture stirred for 2 hours. LCMS showed a small amount of starting material so the reaction was stirred for a further 2 hours. The mixture was then partitioned between EtOAc (20 mL) and water (20 mL) and the organic phase washed with water (20 mL) and brine (20 mL) before it was dried (MgSO4), filtered and the solvent removed in vacuo. The crude product was purified by MDAP. The compound-containing fractions were concentrated and dried in a vacuum oven to give E20 (23 mg) as a white solid, 1H NMR (d6-DMSO) δ 11.62 (1H, s), 8.39 (1H, d), 8.26 (1H, s), 7.88 (2H, d), 7.52 (1H, t), 7.46 (2H, t), 7.09 (1H, s), 4.05 (1H, m), 3.90 (2H, d), 3.16 (1H, septet), 3.00 (2H, t), 1.94 (2H, d), 1.77 (2H, ddd), 1.28 (6H, d), MS(ES+) 364 [M+H]+.

Workup

  1. stirringwas stirred for a further 2 hours
  2. customThe mixture was then partitioned between EtOAc (20 mL) and water (20 mL)
  3. washthe organic phase washed with water (20 mL) and brine (20 mL) before it
  4. dry with materialwas dried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customThe crude product was purified by MDAP
  8. concentrationThe compound-containing fractions were concentrated
  9. customdried in a vacuum oven
  10. customto give E20 (23 mg) as a white solid, 1H NMR (d6-DMSO) δ 11.62 (1H, s), 8.39 (1H, d), 8.26 (1H, s), 7.88 (2H, d), 7.52 (1H, t), 7.46 (2H, t), 7.09 (1H, s), 4.05 (1H, m), 3.90 (2H, d), 3.16 (1H, septet), 3.00 (2H, t), 1.94 (2H, d), 1.77 (2H, ddd), 1.28 (6H, d), MS(ES+) 364 [M+H]+

Sources & evidence

ORD record
ord-c11721e58c6f48edb1bf3a5f3c002558
Source dataset
uspto-grants-2015_06
Patent number
US09045485B2

Reaction notes

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