Lithium Hydroxide → 1-[5-[2-(Ethylcarbamoylamino)-7-(4-methyl-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid

HRID 712256Notes

Reaction equation

HRID 712256 reaction equation
[CH2:1]([NH:3][C:4](=[O:40])[NH:5][C:6]1[S:7][C:8]2[C:14]([C:15]3[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][N:16]=3)=[CH:13][C:12]([C:22]3[CH:23]=[N:24][C:25]([N:28]4[CH2:33][CH2:32][C:31]([CH3:39])([C:34]([O:36]CC)=[O:35])[CH2:30][CH2:29]4)=[N:26][CH:27]=3)=[CH:11][C:9]=2[N:10]=1)[CH3:2].[Li+].[OH-]>C1COCC1>[CH2:1]([NH:3][C:4]([NH:5][C:6]1[S:7][C:8]2[C:14]([C:15]3[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][N:16]=3)=[CH:13][C:12]([C:22]3[CH:27]=[N:26][C:25]([N:28]4[CH2:29][CH2:30][C:31]([CH3:39])([C:34]([OH:36])=[O:35])[CH2:32][CH2:33]4)=[N:24][CH:23]=3)=[CH:11][C:9]=2[N:10]=1)=[O:40])[CH3:2]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 86663970Ethyl 1-(5-(2-(3-ethylureido)-7-(4-methylpyridin-2-yl)benzothiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

Product 1

HCID 569532111-[5-[2-(Ethylcarbamoylamino)-7-(4-methyl-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acidYield 36.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To an ice-cold solution of ethyl 1-(5-(2-(3-ethylureido)-7-(4-methylpyridin-2-yl)benzothiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate (0.015 g, 0.026 mmol) in THF was added aqueous LiOH (0.006 g, 0.134 mmol dissolved in minimum amount of H2O) and the mixture heated up to 65° C. for 3 h. After reaction completion (by TLC), the solvent was concentrated and 10 mL of water added and washed with EtOAc (2×50 mL). The organic layer was discarded and the pH of the aqueous layer was adjusted up to 4-5 then extracted with hot EtOAc (3×50 mL) and the combined organic layer dried over Na2SO4 and solvent evaporated under reduced pressure. The residue thus obtained was triturated with ether to afford the desired product as an off-white solid (0.005 g, 35%). 1H NMR (DMSO-d6): δ 1.11 (t, J=7.20 Hz, 3H), 1.19 (s, 3H), 1.41 (m, 2H), 2.07 (m, 2H), 2.45 (s, 3H), 3.17-3.24 (m, 4H), 4.32 (m, 2H), 6.93 (br s, 1H), 7.27 (d, J=4.80, 1H), 7.94 (s, 1H), 8.23 (s, 1H), 8.35 (s, 1H), 8.65 (d, J=4.8 Hz, 1H), 8.91 (s, 2H) and 10.60 (br s, 1H). MS: 530.21 [M−H]−.

Workup

  1. customAfter reaction completion (by TLC)
  2. concentrationthe solvent was concentrated
  3. addition10 mL of water added
  4. washwashed with EtOAc (2×50 mL)
  5. extractionthen extracted with hot EtOAc (3×50 mL)
  6. dry with materialthe combined organic layer dried over Na2SO4 and solvent
  7. customevaporated under reduced pressure
  8. customThe residue thus obtained
  9. customwas triturated with ether

Sources & evidence

ORD record
ord-b255a882ad1b49bc8cc83d1d52cbd7fb
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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