1,2-Dichloroethane → HCID 11384823, compound

HRID 2373913Notes

Reaction equation

HRID 2373913 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8](C3CCC3)=[N:9][C:10]=2[C:11]2[CH:12]=[C:13]([CH:25]=[CH:26][CH:27]=2)[O:14][CH2:15][C:16]2[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=2)[C:19](O)=[O:20])[CH:5]=[CH:6][N:7]=1.Cl.CN.C[CH2:36][N:37](C(C)C)C(C)C.[CH:44]1C=CC2N(O)N=NC=2[CH:49]=1.[CH2:54](Cl)[CH2:55]Cl>CN(C=O)C>[NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:55]3[CH2:54][CH2:49][CH2:44]3)=[N:9][C:10]=2[C:11]2[CH:12]=[C:13]([CH:25]=[CH:26][CH:27]=2)[O:14][CH2:15][C:16]2[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=2)[C:19]([NH:37][CH3:36])=[O:20])[CH:5]=[CH:6][N:7]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 11418548HCID 11418548, compound

Product 1

HCID 11384823HCID 11384823, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 3-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxymethyl]-benzoic acid (100 mg, 0.24 mmol) and methylamine HCl (163 mg, 2.41 mmol) in DMF (1.2 mL) was charged with DIEA (0.42 mL, 2.41 mmol), HOBt (37.0 mg, 0.24 mmol), and EDC (69.0 mg, 0.36 mmol). The brown colored reaction mixture was allowed to stir for 18 h. LC/MS analysis indicated that the reaction was nearly complete. The reaction was heated to 50° C. and allowed to react for an additional 18 h. The DMF was removed in vacuo and the product was chromatographed on silica gel [Jones Flashmaster, 5 g cartridge, eluting with 2% 7N NH3 MeOH:CH2Cl2] to yield the title compound as a pink solid; 1H NMR (CDCl3, 400 MHz) δ 1.99-2.07 (m, 1H), 2.11-2.20 (m, 1H), 2.44-2.50 (m, 2H), 2.57-2.67 (m, 2H), 3.01 (d, J=5.2 Hz, 3H), 3.76-3.85 (m, 1H), 5.17 (s, 2H), 6.99-7.02 (m, 2H), 7.10 (d, J=5.2 Hz, 1H), 7.24-7.27 (m, 2H), 7.37-7.46 (m, 2H), 7.55 (d, J=7.6 Hz, 1H), 7.71 (d, J=7.6 Hz, 1H), 7.85 (s, 1H); MS (ES+): m/z 428.17 (100) [MH+].

Workup

  1. customto react for an additional 18 h
  2. customThe DMF was removed in vacuo
  3. customthe product was chromatographed on silica gel [Jones Flashmaster, 5 g cartridge, eluting with 2% 7N NH3 MeOH:CH2Cl2]

Sources & evidence

ORD record
ord-c17bbc66cb934bb1a134b19413354d3c
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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