Sodium hydride → US9777003, Example 13

HRID 628259Notes

Reaction equation

HRID 628259 reaction equation
[H-].[Na+].[CH3:3][C:4]1[N:8]2[C:9]3[CH:15]=[C:14]([CH3:16])[NH:13][C:10]=3[CH:11]=[CH:12][C:7]2=[N:6][N:5]=1.I[CH2:18][CH:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1>CN(C=O)C>[CH:19]1([CH2:18][N:13]2[C:10]3[CH:11]=[CH:12][C:7]4[N:8]([C:4]([CH3:3])=[N:5][N:6]=4)[C:9]=3[CH:15]=[C:14]2[CH3:16])[CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 2762531(Iodomethyl)cyclopentane2×HCID 1369631111,7-dimethyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine

Product 1

HCID 118159502US9777003, Example 13

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (13 mg, 0.32 mmol, 60% in mineral oil) was added to a solution of 1,7-dimethyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine (20 mg, 0.1 mmol, from Example 2, Step 5) in DMF (3.0 mL). After stirring for 15 minutes, (iodomethyl)cyclopentane (0.022 g, 0.11 mmol, Acros) was added. After stirring for 45 minutes at room temperature, excess NaH (13 mg, 0.32 mmol, 60% in mineral oil) and (iodomethyl)cyclopentane (0.022 g, 0.11 mmol) were added and the reaction was continued for 20 minutes and then was quenched by the addition of water and diluted to 5 mL volume with MeCN. The resulting solution was filtered and purified by preparative HPLC-MS (Waters XBridge C18, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH) (4 mg, 10%).

Workup

  1. stirringAfter stirring for 45 minutes at room temperature
  2. waitthe reaction was continued for 20 minutes
  3. customwas quenched by the addition of water
  4. additiondiluted to 5 mL volume with MeCN
  5. filtrationThe resulting solution was filtered
  6. custompurified by preparative HPLC-MS (Waters XBridge C18
  7. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH) (4 mg, 10%)

Sources & evidence

ORD record
ord-bb1b512f57db405f9e5e455497c33705
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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