Dimethyl Sulfoxide → HCID 178498839, compound

HRID 707364Notes

Reaction equation

HRID 707364 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][N:15]=[C:10]3[N:9]([CH:16]3[CH2:18][CH2:17]3)[C:8]2=[O:19])[CH2:4]1.ClC1SC=C([C:26]([O:28][CH3:29])=[O:27])N=1.C([N:33]([CH:36]([CH3:38])C)[CH2:34]C)(C)C.C[S:40](C)=O>O>[CH:16]1([N:9]2[C:10]3[C:11](=[N:12][CH:13]=[CH:14][N:15]=3)[N:7]([C@H:5]3[CH2:6][C@H:3]([NH:2][C:34]4[S:40][C:38]([C:26]([O:28][CH3:29])=[O:27])=[CH:36][N:33]=4)[CH2:4]3)[C:8]2=[O:19])[CH2:17][CH2:18]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 7213135Methyl 2-chloro-4-thiazolecarboxylateHCID 178479284HCID 178479284, compound2×

Product 1

HCID 178498839HCID 178498839, compoundYield 27.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 1-(trans-3-aminocyclobutyl)-3-cyclopropyl-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride (Intermediate 79, 1.00 g, 3.55 mmol), methyl 2-chloro-4-thiazolecarboxylate (0.820 g, 4.61 mmol), and diisopropylethylamine (3.09 mL, 17.75 mmol) in DMSO (10 mL) was stirred at 120° C. for 18 h. The reaction was allowed to cool to room temperature, diluted with water and extracted with EtOAc. EtOAc was concentrated and residue purified with ISCO using silica gel column eluting with 0-70% EtOAc/hexane to give the title compound methyl 2-((trans-3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-1-yl)cyclobutyl)amino)thiazole-5-carboxylate (0.380 g, 0.983 mmol, 27.7% yield). m/z: 387.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ: ppm 8.38 (d, J=6.46 Hz, 1 H), 7.99 (q, J=3.26 Hz, 2 H), 7.60 (s, 1 H), 5.15 (t, J=8.31 Hz, 1 H), 4.28-4.47 (m, 1 H), 3.77 (s, 3 H), 3.18-3.30 (m, 2 H), 2.88-3.07 (m, 1 H), 2.34-2.47 (m, 2 H), 0.91-1.13 (m, 4 H).

Workup

  1. extractionextracted with EtOAc
  2. concentrationEtOAc was concentrated
  3. customresidue purified with ISCO
  4. washeluting with 0-70% EtOAc/hexane

Sources & evidence

ORD record
ord-a5aea8449a054be9b1bca879b00ab681
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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