Water → 1-[5-[7-Bromo-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid

HRID 712163Notes

Reaction equation

HRID 712163 reaction equation
[Br:1][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]([CH3:34])([C:29]([O:31]CC)=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)[CH:3]=1.CC(C)([O-])C.[K+].O>CS(C)=O>[Br:1][C:2]1[C:10]2[S:9][C:8]([NH:11][C:12](=[O:13])[NH:14][CH2:15][CH3:16])=[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]([CH3:34])([C:29]([OH:31])=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 86663956Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

Product 1

HCID 866639571-[5-[7-Bromo-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acidYield 88.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To an ice-cold solution of ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzothiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate (25 g, 45.7 mmol) in DMSO (50 mL) was added potassium tert-butoxide (25.5 g, 228 mmol). The resulting mixture was stirred at rt for 1 h. After completion of reaction (by TLC), water (250 mL) was added followed by extraction with EtOAc (2×250 mL). The organic layer was discarded; the pH of the aqueous layer was adjusted up to 4-5 and then extracted with hot EtOAc (3×250 mL). The combined organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure. The residue thus obtained was triturated with ether to obtain the desired product as off-white solid (21 g, 88%). 1H NMR (DMSO-d6): δ 1.09 (t, J=7.20 Hz, 3H), 1.18 (s, 3H), 1.41 (m, 2H), 2.02 (m, 2H), 3.20 (m, 2H), 3.33 (m, 2H), 4.29 (m, 2H), 6.80 (br s, 1H), 7.70 (s, 1H), 7.87 (s, 1H), 8.76 (s, 2H), 10.95 (br s, 1H) and 12.46 (br, s, 1H). MS: 519.19 [M+H]+.

Workup

  1. additionwas added
  2. extractionfollowed by extraction with EtOAc (2×250 mL)
  3. extractionextracted with hot EtOAc (3×250 mL)
  4. dry with materialThe combined organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residue thus obtained
  8. customwas triturated with ether

Sources & evidence

ORD record
ord-049511ff335f451898cb1acc53bcbdd1
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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