Methane → HCID 178430826, compound

HRID 1892122Notes

Reaction equation

HRID 1892122 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[N:17][C:18]#[N:19])OC2C=CC=CC=2)[CH:5]=[CH:6][CH:7]=1.[CH3:20][C:21]1[C:29]2[C:28]([N:30]3[CH2:35][CH2:34][NH:33][C@@H:32]([CH3:36])[CH2:31]3)=[N:27][CH:26]=[N:25][C:24]=2[NH:23][CH:22]=1.C(N(CC)CC)C.C>CC#N.CO>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([N:33]2[CH2:34][CH2:35][N:30]([C:28]3[C:29]4[C:21]([CH3:20])=[CH:22][NH:23][C:24]=4[N:25]=[CH:26][N:27]=3)[CH2:31][C@@H:32]2[CH3:36])=[N:17][C:18]#[N:19])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 297MethaneHCID 8471TriethylamineHCID 68958720HCID 68958720, compoundHCID 178512244HCID 178512244, compound

Product 1

HCID 178430826HCID 178430826, compoundYield 60.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

The cyanocarbamimidate from step A (9.48 g, 30 mmol), (S)-5-methyl-4-(3-methylpiperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine from Example 1, step B (6.93 g, 30 mmol), and triethylamine (4.16 ml, 30 mmol) were combined in MeCN (250 ml) and heated to 85° C. for 6 hours. The reaction was cooled to room temperature and concentrated under vacuum. The residue was purified by flash chromatography (750 g SiO2, 0-7% MeOH:CH2Cl2) to give a yellow foam. This material was dissolved in MeOH and stirred with activated charcoal at 60° C. for 15 min. The mixture was filtered through celite, washing with copious amounts of MeOH and 10% MeOH:CH2Cl2, and concentrated under vacuum. The residue was purified again by flash chromatography (750 g SiO2, 0-7% MeOH:CH2Cl2). The resulting material was dissolved in MeOH, and water was added to crash out the product. The mixture was concentrated under vacuum, and the product was resuspended in water and lyophilized to give a hydrate of (S)—N-(3-bromophenyl)-N′-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide (8.17 g, 57%, 1.25 eq. H2O based on CHN analysis) as an amorphous white solid.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. concentrationconcentrated under vacuum
  3. customThe residue was purified by flash chromatography (750 g SiO2, 0-7% MeOH:CH2Cl2)
  4. customto give a yellow foam
  5. filtrationThe mixture was filtered through celite
  6. washwashing with copious amounts of MeOH and 10% MeOH
  7. concentrationCH2Cl2, and concentrated under vacuum
  8. customThe residue was purified again by flash chromatography (750 g SiO2, 0-7% MeOH:CH2Cl2)
  9. dissolutionThe resulting material was dissolved in MeOH
  10. additionwater was added
  11. concentrationThe mixture was concentrated under vacuum

Sources & evidence

ORD record
ord-47f6ca118fa743ff91300b8da4d8641c
Source dataset
uspto-grants-2013_08
Patent number
US08507672B2

Reaction notes

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