Sodium hydride → HCID 70215340, compound

HRID 2047025Notes

Reaction equation

HRID 2047025 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.[H-].[Na+].Cl[C:19]1[CH:24]=[C:23]([N:25]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:22]2[N:42]=[CH:43][C:44]([C:45]3[CH:46]=[N:47][C:48]4[C:53]([CH:54]=3)=[CH:52][CH:51]=[CH:50][CH:49]=4)=[C:21]2[N:20]=1.[Br:55]N1C(=O)CCC1=O>C1COCC1.C(OCC)(=O)C>[CH3:31][Si:30]([CH3:33])([CH3:32])[CH2:29][CH2:28][O:27][CH2:26][N:25]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[C:23]1[N:22]2[N:42]=[CH:43][C:44]([C:45]3[CH:46]=[N:47][C:48]4[C:53]([CH:54]=3)=[CH:52][CH:51]=[CH:50][CH:49]=4)=[C:21]2[N:20]=[C:19]([O:1][CH2:2][CH:3]2[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]2)[C:24]=1[Br:55]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 67184N-bromobutanimideHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 86664780(5-Chloro-3-quinolin-3-yl-pyrazolo[1,5-a]pyrimidin-7-yl)-bis-(2-trimethylsilanyl-ethoxymethyl)-amine

Product 1

HCID 70215340HCID 70215340, compoundYield 95.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (311 mg, 1.44 mmol) and sodium hydride (60% in mineral oil, 58 mg, 1.44 mmol) in THF (2 ml) under argon at room temperature was added 5-chloro-3-(quinolin-3-yl)-N,N-bis((2(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (400 mg, 0.72 mmol). The mixture was heated at 100° C. for 30 min in microwave. Ethyl acetate (50 ml) was added and the mixture was washed with brine and water, dried over Na2SO4, and concentrated in vacuo. The crude product was dissolved in acetonitrile, followed by the addition of N-bromosuccinimide (193 mg, 1.08 mmol). The reaction mixture was stirred at room temperature for 2 h, concentrated in vacuo and purified via silica gel chromatography (10% to 50% ethyl acetate in hexanes gradient) to yield the title compound (0.56 g, 95% yield). LC-MS: 813 [M+H].

Workup

  1. washthe mixture was washed with brine and water
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. dissolutionThe crude product was dissolved in acetonitrile
  5. concentrationconcentrated in vacuo
  6. custompurified via silica gel chromatography (10% to 50% ethyl acetate in hexanes gradient)

Sources & evidence

ORD record
ord-14df657f0b90484d8338166944f2cc2c
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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