Dichloromethane → HCID 53629051, compound

HRID 244139Notes

Reaction equation

HRID 244139 reaction equation
ClC1C([NH:8][CH2:9][C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][C:14]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:13]3)=NC=CN=1.[CH:26]1([C:30]([OH:32])=O)[CH2:29][CH2:28][CH2:27]1.C1C=[C:37]2[N:39]=N[N:41](O)[C:36]2=CC=1.O.C(N([CH2:51][CH3:52])C(C)C)(C)C.C(Cl)[Cl:54]>C(Cl)CCl>[Cl:54][C:51]1[C:52]([CH:9]([C:10]2[CH:19]=[C:18]3[C:17](=[CH:12][CH:11]=2)[N:16]=[CH:15][C:14]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:13]3)[NH:8][C:30]([CH:26]2[CH2:27][CH2:28][CH2:29]2)=[O:32])=[N:41][CH:36]=[CH:37][N:39]=1

Participants

7

Reactant 5

HCID 6344Dichloromethane2×HCID 19494Cyclobutanecarboxylic acidHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 86608527HCID 86608527, compound

Product 1

HCID 53629051HCID 53629051, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

(3-Chloropyrazin-2-yl)(3-phenylquinoxalin-6-yl)methyl-amine (106 mg, 0.30 mmol) and cyclobutanecarboxylic acid (51 mg, 0.46 mmol) were dissolved in DCM (10 mL). EDC (93 mg, 0.49 mmo) and HOBt hydrate (62 mg, 0.46 mmol) were added in sequence followed by N,N-diisopropylethylamine (0.15 mL, 0.83 mmol). The reaction was stirred at rt under Ar for 24 h then evaporated to dryness and purified by flash chromatography (0-1.5% MeOH in DCM) to afford a reddish oil. The material was dissolved in DCM (50 mL), washed with satd NaHCO3 (2×), H2O (1×), brine (1×), dried (MgSO4) and concentrated under reduced pressure (light yellow oil). Purification by flash chromatography (silica gel, 33% to 65% EtOAc in hexanes) afforded the title compound as a white solid; 1H NMR (400 MHz, CD3CN) δ 9.40 (s, 1H), 8.60 (d, J=2.8 Hz, 1H), 8.39 (d, J=2.4 Hz, 1H), 8.30-8.25 (m, 2H), 8.06 (d, J=8.4 Hz, 1H), 8.02 (s, 1H), 7.80 (dd, J=2.0 Hz, 8.8 Hz, 1H), 7.85-7.75 (m, 3H), 7.51 (d, J=7.8 Hz, 1H), 6.77 (d, J=8.0 Hz, 1H), 3.20 (quintet, J=8.4 Hz, 1H), 2.25-2.05 (m, 4H), 1.85-1.75 (m, 2H).). MS (ES+): m/z 430.0 (100) [MH+]; HPLC: tR=3.40 min (OpenLynx, polar—5 min).

Workup

  1. customthen evaporated to dryness
  2. custompurified by flash chromatography (0-1.5% MeOH in DCM)
  3. customto afford a reddish oil
  4. washwashed with satd NaHCO3 (2×), H2O (1×), brine (1×)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure (light yellow oil)
  7. customPurification by flash chromatography (silica gel, 33% to 65% EtOAc in hexanes)

Sources & evidence

ORD record
ord-cfce6e5a2cab4e79b2697f2ebb92d866
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

Loading…