Triethylamine → HCID 66991259, compound

HRID 2365752Notes

Reaction equation

HRID 2365752 reaction equation
CO[C:3](=[C:14]([C:17]#[N:18])[C:15]#[N:16])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-:13])=[O:12])[CH:6]=1.Cl.[C:20]([NH:24][NH2:25])([CH3:23])([CH3:22])[CH3:21].C(N(CC)CC)C>CCO>[N+:11]([C:7]1[CH:6]=[C:5]([CH:10]=[CH:9][CH:8]=1)[CH2:4][C:3]1[C:14]([C:15]#[N:16])=[C:17]([NH2:18])[N:24]([C:20]([CH3:23])([CH3:22])[CH3:21])[N:25]=1)([O-:13])=[O:12]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 81889tert-Butylhydrazine monohydrochlorideHCID 86659132HCID 86659132, compound

Product 1

HCID 66991259HCID 66991259, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Reagent 2-(1-methoxy-2-(3-nitrophenyl)ethylidene)malononitrile (1.2 g; 4.7 mmol) was combined with tert-butylhydrazine-HCl (0.57 g; 5.2 mmol; Sigma-Aldrich), 1.4 mL triethylamine in 50 mL EtOH for at 2 hours at 80° C. The reaction was concentrated in vacuo, resuspended in brine and extracted with chloroform. The organic layer was dried over MgSO4. Following, the organic suspension was filtered, concentrated in vacuo, and purified on silica gel in 1% MeOH:CHCl3 to yield 3-(3-nitrobenzyl)-1-tert-butyl-5-amino-1H-pyrazole-4-carbonitrile (ESI-MS m/z [M−CH3]+ found 285.5, calculated 285.14; 1H NMR (400 MHz, DMSO): δ8.11 (s, 1H), 8.08-8.12 (m, 1H), 7.69 (d, J=8 Hz, 1H), 7.59-7.64 (m, 1H), 3.96 (s, 2H), 3.34 (br, 2H), 1.52 (s, 9H)). This product was combined with formamide as per Cmpd 1 to yield 3-(3-nitrobenzyl)-1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (ESI-MS m/z [M+H]+ found 327.4, calculated 327.15; 1H NMR (400 MHz, DMSO): δ 8.22 (s, 1H), 8.14 (s, 1H), 8.07 (d, J=8 Hz, 1H), 7.67 (d, J=8 Hz, 1H), 7.59 (d, J=8 Hz, 1H), 7.22 (br, 2H), 4.52 (s, 2H), 1.70 (s, 9H)). Reduction of this material was completed as per Cmpd 1 to yield 3-(3-aminobenzyl)-1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (ESI-MS m/z [M+H]+ found 297.13, calculated 297.17). The reduced precursor was coupled to 3-(trifluoromethyl)phenyl isocyanate and purified as described for Cmpd 1 to yield Cmpd 4 1-(3-((1-tert-butyl-4-amino-1H-pyrazolo[3,4-d]pyrimidin-3-yl)methyl)phenyl)-3-(3-(trifluoromethyl)phenyl)urea (ESI-MS m/z [M+H]+ found 484.5, calculated 484.2; 1H NMR (400 MHz, DMSO): δ 9.25 (s, 1H), 8.96 (s, 1H), 8.32 (s, 1H), 8.06 (s, 1H), 7.46-7.55 (m, 2H), 7.40 (s, 1H), 7.29 (d, J=8 Hz, 2H), 7.20 (t, J=8 Hz, 1H), 6.89 (d, J=8 Hz, 1H), 4.39 (s, 2H), 1.73 (s, 9H). 13C NMR (400 MHz, DMSO): δ 29.25, 33.40, 60.74, 99.58, 116.43 (d), 116.95, 118.86, 122.13, 122.64, 124.69 (q), 129.29, 129.98 (q), 130.32, 139.60, 140.06, 141.16, 143.31, 149.70, 152.69, 152.92, 154.81, 159.12 (q)).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. extractionextracted with chloroform
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationthe organic suspension was filtered
  5. concentrationconcentrated in vacuo
  6. custompurified on silica gel in 1% MeOH

Sources & evidence

ORD record
ord-e5c2dee18efe4d17b7b555852b932ebf
Source dataset
uspto-grants-2014_04
Patent number
US08697709B2

Reaction notes

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