Sodium hydride → 4-(7-Methoxy-thiazolo[5,4-d]pyrimidin-2-ylcarbamoyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 550809Notes

Reaction equation

HRID 550809 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[N:11]=[C:10]([NH2:12])[S:9][C:5]=2[N:6]=[CH:7][N:8]=1.[H-].[Na+].C(N(CC)C(C)C)(C)C.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][N:34]([C:37](Cl)=[O:38])[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]>O1CCCC1>[C:24]([O:28][C:29]([N:31]1[CH2:32][CH2:33][N:34]([C:37](=[O:38])[NH:12][C:10]2[S:9][C:5]3[N:6]=[CH:7][N:8]=[C:3]([O:2][CH3:1])[C:4]=3[N:11]=2)[CH2:35][CH2:36]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 11334154Tert-butyl 4-(chlorocarbonyl)piperazine-1-carboxylateHCID 574765977-Methoxy-[1,3]thiazolo[5,4-d]pyrimidin-2-amine

Product 1

HCID 590119304-(7-Methoxy-thiazolo[5,4-d]pyrimidin-2-ylcarbamoyl)-piperazine-1-carboxylic acid tert-butyl esterYield 74.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of 7-methoxy-thiazolo[5,4-d]pyrimidin-2-ylamine (3.5 g, 19.2 mmol) in tetrahydrofuran (100 mL) was treated with sodium hydride (60% in mineral oil, 2.3 g, 57 mmol) at 25° C. A slight evolution of gas was observed. The resulting purple slurry was warmed to 50° C. for 1 h. At this time, the reaction was cooled to 25° C. and was treated with N,N-diisopropylethylamine (10 mL, 57 mmol). The resulting mixture was stirred at 25° C. for 30 min. The mixture was then treated with a solution of 4-chlorocarbonyl-piperazine-1-carboxylic acid tert-butyl ester (4.73 g, 19 mmol) in tetrahydrofuran (20 mL) over a 10 min period. The reaction was stirred at 50° C. overnight. At this time, the reaction was concentrated in vacuo, diluted with methanol (100 mL) and absorbed onto silica gel (6 g). The silica gel was divided into two equal lots. ISCO chromatography (330 g, Silica, gradient elution 5/95 methanol/methylene chloride) afforded 4-(7-methoxy-thiazolo[5,4-d]pyrimidin-2-ylcarbamoyl)-piperazine-1-carboxylic acid tert-butyl ester (5.58 g, 74%) as an off-white solid; LRMS for C16H22N6O4S (M+H)+ at m/z=395. The NMR spectrum obtained on the sample is compatible with its structure.

Workup

  1. temperatureAt this time, the reaction was cooled to 25° C.
  2. stirringThe reaction was stirred at 50° C. overnight
  3. concentrationAt this time, the reaction was concentrated in vacuo
  4. additiondiluted with methanol (100 mL)
  5. customabsorbed onto silica gel (6 g)
  6. washISCO chromatography (330 g, Silica, gradient elution 5/95 methanol/methylene chloride)

Sources & evidence

ORD record
ord-2ca2cb42ee384d328e68a8ad24956132
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

Loading…