Acetic Acid → 1-{5-[2-(3-Ethyl-ureido)-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid

HRID 712265Notes

Reaction equation

HRID 712265 reaction equation
Br[C:2]1[C:10]2[S:9][C:8]([NH:11][C:12]([NH:14][CH2:15][CH3:16])=[O:13])=[N:7][C:6]=2[CH:5]=[C:4]([C:17]2[CH:18]=[N:19][C:20]([N:23]3[CH2:28][CH2:27][C:26]([CH3:32])([C:29]([OH:31])=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)[CH:3]=1.C1COCC1.CC(O)=O.C([O-])=O.[NH4+]>CCO.[Pd]>[CH2:15]([NH:14][C:12](=[O:13])[NH:11][C:8]1[S:9][C:10]2[CH:2]=[CH:3][C:4]([C:17]3[CH:18]=[N:19][C:20]([N:23]4[CH2:24][CH2:25][C:26]([CH3:32])([C:29]([OH:31])=[O:30])[CH2:27][CH2:28]4)=[N:21][CH:22]=3)=[CH:5][C:6]=2[N:7]=1)[CH3:16]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 2723923Ammonium formateHCID 866639571-[5-[7-Bromo-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid

Product 1

HCID 569524221-{5-[2-(3-Ethyl-ureido)-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acidYield 38.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

1-{5-[7-Bromo-2-(3-ethyl-ureido)-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid (16 mg) was dissolved in EtOH (5 mL), THF (1 mL) and AcOH (0.5 mL) and 10% palladium on carbon (3 mg) was added followed by ammonium formate (78 mg). The mixture was degassed and heated at 60° C. for four days then cooled to rt. The mixture was filtered through a syringe filter and the filtrate concentrated in vacuo. The material was purified by preperative HPLC (Gilson, 40-60%, water/MeCN+0.1% formic acid). The relevant fractions were combined and freeze-dried overnight to give Compound 46 as a white solid (5.2 mg). 1H NMR ((CD3)2SO): δ 1.09 (3H, t, J=7.2 Hz), 1.13 (3H, s), 1.29 (2H, m), 2.03 (2H, br d, J=13.5 Hz), 3.17 (4H, m), 4.1 (1H, br s), 4.23 (2H, br dt, J=13.5 and 4.7 Hz), 7.43 (1H, dd, J=8.2 and 1.5 Hz), 7.6 (1H, br s), 7.83 (1H, d, J=1.5 Hz), 7.88 (1H, d, J=8.2 Hz), 8.71 (2H, s), 11.5 (1H, br s). m/z: 441 [M+H]+.

Workup

  1. customThe mixture was degassed
  2. temperaturethen cooled to rt
  3. filtrationThe mixture was filtered through a syringe
  4. filtrationfilter
  5. concentrationthe filtrate concentrated in vacuo
  6. customThe material was purified by preperative HPLC (Gilson, 40-60%, water/MeCN+0.1% formic acid)
  7. customfreeze-dried overnight

Sources & evidence

ORD record
ord-41365ece35194493bcc94bca4fc2189c
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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