Picolyl chloride hydrochloride → HCID 67102291, compound

HRID 2079840Notes

Reaction equation

HRID 2079840 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[N:11]=[C:12]4[C:18]([C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:17][N:16]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:13]4=[N:14][CH:15]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Cl.Cl[CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][N:47]=1.C(=O)(O)[O-].[Na+]>CCOC(C)=O.CN(C=O)C>[CH3:21][C:20]([CH3:23])([CH3:22])[C:19]([C:18]1[C:12]2[C:13](=[N:14][CH:15]=[C:10]([C:6]3[CH:5]=[C:4]4[C:9](=[CH:8][CH:7]=3)[N:1]([CH2:45][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][N:47]=3)[CH:2]=[CH:3]4)[N:11]=2)[N:16]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:31])([CH3:30])[CH3:32])[CH:17]=1)=[O:24]

Participants

7

Reactant 4

HCID 23392Picolyl chloride hydrochlorideHCID 516892Sodium BicarbonateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 57829224HCID 57829224, compound

Product 1

HCID 67102291HCID 67102291, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a DMF (1 mL) solution of 1-[2-(1H-Indol-5-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (50 mg, 0.11 mmol; prepared as described in Ex. 45, only using the Sem-protected starting material) was added NaHMDS (0.25 mL, 1M in THF) and stirred for 20 min at RT. 2-Chloromethylpyridine hydrochloride (21.6 mg, 0.13 mmol) was added in a single portion. After stirring for 1 hr at RT TLC analysis (25% EtOAc/hexanes) shows a new more-polar product. The reaction mixture was poured into 25 mL of saturated sodium bicarbonate solution and extracted with EtOAc (2×15 mL). The organic layers were combined, washed with brine, dried over MgSO4, and concentrated to give a yellow oil. Chromatography (SiO2; 0%-13%-25% EtOAc in hexanes) gives 2,2-Dimethyl-1-[2-(1-pyridin-2-ylmethyl-1H-indol-5-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one as a clear oil. Following general deprotection procedures as described in these Examples, the SEM group was removed to give 2,2-Dimethyl-1-[2-(1-pyridin-2-ylmethyl-1H-indol-5-yl)-5Hpyrrolo[2,3-b]pyrazin-7-yl]propan-1-one (47%; MS=410 [M+H]; MP: 194-196° C.).

Workup

  1. customprepared
  2. extractionextracted with EtOAc (2×15 mL)
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customto give a yellow oil

Sources & evidence

ORD record
ord-435bb13e0bb34d878f8385724a247a23
Source dataset
uspto-grants-2011_04
Patent number
US07932254B2

Reaction notes

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