Ethylenediamine → HCID 86651907, compound

HRID 1772831Notes

Reaction equation

HRID 1772831 reaction equation
[C:1]([CH2:3][CH:4]([N:25]1[CH:29]=[C:28]([C:30]2[C:31]3[CH:38]=[CH:37][N:36](COCC[Si](C)(C)C)[C:32]=3[N:33]=[CH:34][N:35]=2)[CH:27]=[N:26]1)[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2[CH:21]=[CH:20][C:17](C#N)=[CH:16][C:15]=2[F:22])=[O:13])[CH2:8][CH:7]1[CH2:23]O)#[N:2].[C:47]([OH:53])([C:49]([F:52])([F:51])[F:50])=[O:48].C(N)CN>C(Cl)Cl>[F:50][C:49]([F:52])([F:51])[C:47]([OH:53])=[O:48].[F:50][C:49]([F:52])([F:51])[C:47]([OH:53])=[O:48].[F:22][C:15]1[CH:16]=[C:17]([OH:48])[CH:20]=[CH:21][C:14]=1[C:12]([N:9]1[CH2:8][CH2:7][CH2:23][N:6]([CH2:5][CH:4]([N:25]2[CH:29]=[C:28]([C:30]3[C:31]4[CH:38]=[CH:37][NH:36][C:32]=4[N:33]=[CH:34][N:35]=3)[CH:27]=[N:26]2)[CH2:3][C:1]#[N:2])[CH2:11][CH2:10]1)=[O:13]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 67272963HCID 67272963, compound

Product 1

HCID 86651907HCID 86651907, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-{[4-{3-cyano-2-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}-3-(hydroxymethyl)piperazin-1-yl]carbonyl}-3-fluorobenzonitrile (9 mg, 0.01 mmol; peak 1 from Step 5) was stirred in a solution of 1:1 TFA:DCM (2 mL) for 1 h. Solvents were removed in vacuo. The residue was dissolved in methanol (1.0 mL), and ethylenediamine (0.050 mL, 0.75 mmol) was added. After 30 min, the product was purified via preparative HPLC-MS (C18, eluting first with a gradient of H2O/MeCN containing 0.15% NH4OH, then repurified eluting with a gradient of H2O/MeCN containing 0.1% TFA) and lyophilized to afford product as the (2.66×) trifluoroacetate salt (6.3 mg, 60%). 1H NMR (500 MHz, DMSO-d6, 90° C.): δ 12.11 (br s, 1H), 8.77 (s, 1H), 8.74 (s, 1H), 8.38 (s, 1H), 7.84 (d, 1H), 7.71 (d, 1H), 7.63-7.60 (m, 1H), 7.55 (t, 1H), 6.99 (br d, 1H), 4.92-4.85 (m, 1H), 3.85-2.35 (m, 13H); 19F NMR (400 MHz, DMSO-d6): δ −74.94 (s, 8F), −114.23 to −114.96 (m, 1F); LCMS (M+H)+: 514.2.

Workup

  1. customSolvents were removed in vacuo
  2. dissolutionThe residue was dissolved in methanol (1.0 mL)
  3. customthe product was purified via preparative HPLC-MS (C18
  4. washeluting first with a gradient of H2O/MeCN containing 0.15% NH4OH
  5. customrepurified
  6. washeluting with a gradient of H2O/MeCN containing 0.1% TFA) and

Sources & evidence

ORD record
ord-76133c27eb5b43d486e44b75f334c647
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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