Ethylenediamine → HCID 86666556, compound

HRID 575503Notes

Reaction equation

HRID 575503 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:20][C:21]1[CH:22]=[C:23]([OH:28])[CH:24]=[C:25]([F:27])[CH:26]=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.O[CH:46]1[CH2:51][CH2:50][N:49]([CH2:52][CH:53]([N:57]2[CH:61]=[C:60]([C:62]3[C:63]4[CH:70]=[CH:69][N:68](COCC[Si](C)(C)C)[C:64]=4[N:65]=[CH:66][N:67]=3)[CH:59]=[N:58]2)[CH2:54][C:55]#[N:56])[CH2:48][CH2:47]1.[F:79][C:80]([F:85])([F:84])[C:81]([OH:83])=[O:82].C(N)CN>C1COCC1.C(Cl)Cl.C(#N)C>[F:79][C:80]([F:85])([F:84])[C:81]([OH:83])=[O:82].[F:79][C:80]([F:85])([F:84])[C:81]([OH:83])=[O:82].[F:79][C:80]([F:85])([F:84])[C:81]([OH:83])=[O:82].[F:20][C:21]1[CH:22]=[C:23]([CH:24]=[C:25]([F:27])[CH:26]=1)[O:28][CH:46]1[CH2:47][CH2:48][N:49]([CH2:52][CH:53]([N:57]2[CH:61]=[C:60]([C:62]3[C:63]4[CH:70]=[CH:69][NH:68][C:64]=4[N:65]=[CH:66][N:67]=3)[CH:59]=[N:58]2)[CH2:54][C:55]#[N:56])[CH2:50][CH2:51]1

Participants

10

Reactant 6

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 11776TriphenylphosphineHCID 759283,5-DifluorophenolHCID 97268Di-tert-butyl azodicarboxylateHCID 67956408HCID 67956408, compound

Product 1

HCID 86666556HCID 86666556, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of resin of triphenylphosphine (54.6 mg, 0.114 mmol) in THF (0.6 mL) was added 3,5-difluorophenol (10.1 mg, 0.0778 mmol) and di-tert-butyl azodicarboxylate (19.1 mg, 0.0830 mmol). The mixture was stirred for 15 minutes before adding 4-(4-hydroxypiperidin-1-yl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile (25.0 mg, 0.0519 mmol). The reaction was stirred overnight at room temperature and the solvent was evaporated. The vial and resin were washed with DCM and filtered. The filtrates were washed with 10% aq. NaOH solution. The organic was collected and concentrated to give the crude product. The crude residue was dissolved in methylene chloride (0.20 mL) and trifluoroacetic acid (0.17 mL) was added. The mixture was stirred for 2 hours then concentrated. The residue was dissolved in methanol (0.5 mL) followed by adding ethylenediamine (0.10 mL, 1.50 mmol). After stirring for 1 hour, the mixture was diluted with acetonitrile and purified by preparative LCMS (C18 column eluting with a gradient of acetonitrile (ACN)/H2O containing 0.1% trifluoroacetic acid (TFA)) to afford the desired product (12.6 mg, 30%). 1H NMR (CD3OD) δ9.08 (s, 1H), 8.92 (s, 1H), 8.60 (s, 1H), 7.86 (s, 1H), 7.27 (s, 1H), 6.64 (d, 2H), 6.54 (t, 1H), 5.56 (m, 1H), 4.70 (s, 1H), 4.21 (t, 2H), 3.74 (d, 1H), 3.52 (br, 2H), 3.28 (m, 4H), 2.15 (m, 4H). LCMS (M+H)+: 464.1.

Workup

  1. stirringThe reaction was stirred overnight at room temperature
  2. customthe solvent was evaporated
  3. washThe vial and resin were washed with DCM
  4. filtrationfiltered
  5. washThe filtrates were washed with 10% aq. NaOH solution
  6. customThe organic was collected
  7. concentrationconcentrated
  8. customto give the crude product
  9. stirringThe mixture was stirred for 2 hours
  10. concentrationthen concentrated
  11. dissolutionThe residue was dissolved in methanol (0.5 mL)
  12. stirringAfter stirring for 1 hour
  13. custompurified by preparative LCMS (C18 column
  14. washeluting with a gradient of acetonitrile (ACN)/H2O containing 0.1% trifluoroacetic acid (TFA))

Sources & evidence

ORD record
ord-64f6936a28814336bb7b767f5c158810
Source dataset
uspto-grants-2015_05
Patent number
US09034884B2

Reaction notes

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