7-iodo-5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine → (4-methyl-tetrahydro-thiopyran-4-yl)-[2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-methanol

HRID 1677385Notes

Reaction equation

HRID 1677385 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=3)[N:9]=2)[N:4]([Si](C(C)C)(C(C)C)C(C)C)[CH:3]=1.[Li]CCCC.[CH3:38][C:39]1([CH:45]=[O:46])[CH2:44][CH2:43][S:42][CH2:41][CH2:40]1>O1CCCC1>[CH3:38][C:39]1([CH:45]([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[C:8]([C:11]4[CH:12]=[C:13]([O:21][CH3:22])[C:14]([O:19][CH3:20])=[C:15]([O:17][CH3:18])[CH:16]=4)[N:9]=3)[NH:4][CH:3]=2)[OH:46])[CH2:44][CH2:43][S:42][CH2:41][CH2:40]1

Participants

5

Reactant 3

HCID 595405257-iodo-5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazineHCID 866466834-Formyl-4-methylthianeHCID 178418339Butyllithium

Product 1

HCID 67343380(4-methyl-tetrahydro-thiopyran-4-yl)-[2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-methanolYield 32.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 7-iodo-5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine (400 mg, 0.7 mmol) in anhydrous tetrahydrofuran (5 ml) was cooled to −78° C. and treated with nBuLi (2.23M in hexanes, 0.42 ml, 0.94 mmol) dropwise. The reaction mixture was stirred for 30 seconds and then treated with a solution of 4-methyl-tetrahydro-thiopyran-4-carbaldehyde (0.305 mg, 2.1 mmol) in anhydrous tetrahydrofuran (2 ml), dropwise. The reaction mixture was allowed to stir at −78° C. for 30 minutes. The reaction mixture was partitioned between EtOAc/saturated aqueous NH4Cl. The organic layers were collected, dried over MgSO4, filtered, and concentrated giving a yellowish oil. The oil was purified by silica gel chromatography using 3-100% EtOAc in hexanes as eluant to provide 97 mg (32%) of (4-methyl-tetrahydro-thiopyran-4-yl)-[2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-methanol as a pale yellow solid. M+H=430.

Workup

  1. stirringto stir at −78° C. for 30 minutes
  2. customThe reaction mixture was partitioned between EtOAc/saturated aqueous NH4Cl
  3. customThe organic layers were collected
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customgiving a yellowish oil
  8. customThe oil was purified by silica gel chromatography

Sources & evidence

ORD record
ord-ad0fdfc3adcb49908d94f688e27b69fa
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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