Triethylamine → HCID 178426497, compound

HRID 707358Notes

Reaction equation

HRID 707358 reaction equation
Cl[C:2]1[C:3]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=O)=[N:4][CH:5]=[CH:6][N:7]=1.S(Cl)(Cl)=O.C(N(CC)CC)C.Cl.Cl.Cl.[CH3:28][C:29]1[CH:30]=[CH:31][C:32]([NH:35][C@H:36]2[CH2:39][C@@H:38]([NH2:40])[CH2:37]2)=[N:33][CH:34]=1.CC(C)([O-])C.[Na+]>ClCCCl.C1COCC1.O>[CH3:12][C:8]1([CH3:13])[C:3]2[C:2](=[N:7][CH:6]=[CH:5][N:4]=2)[N:40]([C@H:38]2[CH2:37][C@@H:36]([NH:35][C:32]3[CH:31]=[CH:30][C:29]([CH3:28])=[CH:34][N:33]=3)[CH2:39]2)[C:9]1=[O:11]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 23676156Sodium t-butoxideHCID 866941182-(3-Chloropyrazin-2-yl)-2-methylpropanoic acid2×HCID 178426498HCID 178426498, compound2×

Product 1

HCID 178426497HCID 178426497, compoundYield 59.6%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 2-(3-chloropyrazin-2-yl)-2-methylpropanoic acid (0.200 g, 0.997 mmol), (INTERMEDIATE 29), in DCE (2 mL) was treated with thionyl chloride (2 ml, 27.4 mmol) at room temperature and the resulting solution heated to 60° C. for 1 h and concentrated. The residue obtained was dissolved in THF (5 mL) and triethylamine (0.416 ml, 2.99 mmol) and cis-N1-(5-methylpyridin-2-yl)cyclobutane-1,3-diamine trihydrochloride (INTERMEDIATE 61) (0.314 g, 1.097 mmol) were added. After stirring at room temperature for 30 minutes, sodium tert-butoxide (0.610 ml, 4.98 mmol) was added. The reaction mixture was stirred at room temperature for another 1 h, then diluted with water and extracted with EtOAc. EtOAc was concentrated and residue purified with ISCO eluting with 0-80% EtOAc/hexanes to afford the title compound 7,7-dimethyl-5-(cis-3-((5-methylpyridin-2-yl)amino)cyclobutyl)-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one (0.192 g, 0.594 mmol, 59.6% yield). m/z: 324.2 (M+1); 1H NMR (400 MHz, CHLOROFORM-d) δ; ppm 8.02-8.16 (m, 2 H), 7.93 (d, J=0.78 Hz, 1 H), 7.25-7.31 (m, 2 H), 6.37 (d, J=8.41 Hz, 1 H), 4.99 (d, J=8.41 Hz, 1 H), 4.79 (quin, J=8.71 Hz, 1 H), 4.02-4.26 (m, 1 H), 2.92-3.06 (m, 3 H), 2.74-2.90 (m, 3 H), 2.18 (s, 4 H), 1.44 (s, 8 H).

Workup

  1. concentrationconcentrated
  2. customThe residue obtained
  3. stirringThe reaction mixture was stirred at room temperature for another 1 h
  4. extractionextracted with EtOAc
  5. concentrationEtOAc was concentrated
  6. customresidue purified with ISCO
  7. washeluting with 0-80% EtOAc/hexanes

Sources & evidence

ORD record
ord-97cf2f86ff234dd8ac5033010a65e68f
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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