Sodium hydride → 4-[5-Acetyl-6-(6-methanesulfonyl-pyridin-3-ylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Tert-Butyl Ester

HRID 1036765Notes

Reaction equation

HRID 1036765 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:18]1[C:23]([C:24](=[O:26])[CH3:25])=[C:22]([NH:27][C:28]2[CH:29]=[N:30][C:31]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:32][CH:33]=2)[N:21]=[CH:20][N:19]=1>CN(C)C(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:18]2[C:23]([C:24](=[O:26])[CH3:25])=[C:22]([NH:27][C:28]3[CH:29]=[N:30][C:31]([S:34]([CH3:37])(=[O:35])=[O:36])=[CH:32][CH:33]=3)[N:21]=[CH:20][N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 865973601-[4-Chloro-6-(6-methanesulfonyl-pyridin-3-ylamino)-pyrimidin-5-yl]-ethanone

Product 1

HCID 112488854-[5-Acetyl-6-(6-methanesulfonyl-pyridin-3-ylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Tert-Butyl EsterYield 50.4%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

4-Hydroxy-piperidine-1-carboxylic acid tert-butyl ester (3.2 mmol, 633 mg) and sodium hydride (3.2 mmol, 76 mg) were dissolved in N,N-dimethyl acetamide (1.5 mL) and stirred for 30 minutes at room temperature. Subsequently, compound 1-[4-chloro-6-(6-methanesulfonyl-pyridin-3-ylamino)-pyrimidin-5-yl]-ethanone (0.63 mmol, 207 mg) was added. The reaction was stirred at 70° C. for 30 minutes. Progress of the reaction was monitored by thin layer chromatography and LCMS. Sodium hydride was carefully quenched with water and the desired compound was extracted with ethyl acetate. Organic solvents were evaporated in vacuo and purified by flash chromatography (Silica gel 60; 50/50 EtoAc/Hexanes) to afford Compound A37 as a yellow solid (156 mg, 50%). 1H NMR (400 MHz, CDCl3) δ (ppm): 12.19 (s, 1H), 8.95 (s, 1H), 8.56 (d, 1H), 8.44 (s, 1H), 8.07 (d, 1H), 5.56 (h, 1H), 3.82 (m, 2H), 3.31 (m, 2H), 3.23 (s, 3H), 2.70 (s, 3H), 2.11 (m, 2H), 1.85 (m, 2H), 1.48 (s, 9H). LCMS (ESI), m/z 492.4 (M+H+, 100%).

Workup

  1. stirringThe reaction was stirred at 70° C. for 30 minutes
  2. customSodium hydride was carefully quenched with water
  3. extractionthe desired compound was extracted with ethyl acetate
  4. customOrganic solvents were evaporated in vacuo
  5. custompurified by flash chromatography (Silica gel 60; 50/50 EtoAc/Hexanes)

Sources & evidence

ORD record
ord-afd4cd2033e64fd7a281438339dfc5b5
Source dataset
uspto-grants-2013_10
Patent number
US08546429B2

Reaction notes

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