1,2-Dichloroethane → HCID 16660148, compound

HRID 2097096Notes

Reaction equation

HRID 2097096 reaction equation
C(Cl)CCl.Cl.[NH2:6][C:7]1[N:12]=[CH:11][C:10](/[CH:13]=[CH:14]/[C:15]([OH:17])=O)=[CH:9][C:8]=1[C:18]([OH:21])([CH3:20])[CH3:19].C1C=CC2N(O)N=NC=2C=1.[CH3:32][NH:33][CH2:34][C:35]1[N:36]([CH3:44])[C:37]2[C:42]([CH:43]=1)=[CH:41][CH:40]=[CH:39][CH:38]=2.C(N(C(C)C)C(C)C)C>CN(C=O)C.O>[NH2:6][C:7]1[N:12]=[CH:11][C:10](/[CH:13]=[CH:14]/[C:15]([N:33]([CH3:32])[CH2:34][C:35]2[N:36]([CH3:44])[C:37]3[C:42]([CH:43]=2)=[CH:41][CH:40]=[CH:39][CH:38]=3)=[O:17])=[CH:9][C:8]=1[C:18]([OH:21])([CH3:20])[CH3:19]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11401058methyl((1-methyl-1H-indol-2-yl)methyl)amineHCID 66967079HCID 66967079, compound

Product 1

HCID 16660148HCID 16660148, compoundYield 16.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
35 °C

Procedure

EDC (0.13 g, 0.70 mmol) was added to a suspension of (E)-3-[6-Amino-5-(1-hydroxy-1-methyl-ethyl)-pyridin-3-yl]-acrylic acid hydrochloride (0.15 g, 0.58 mmol), HOBt (0.09 g, 0.64 mmol), Methyl-(1-methyl-1H-indol-2-ylmethyl)-amine (0.11 g, 0.64 mmol) and (i-Pr)2EtN (0.49 mL, 2.9 mmol) in DMF (8 mL). The mixture was allowed to stir overnight at 35° C. The mixture was cooled to 0° C. and diluted with H2O (60 mL) with rapid stirring. The resulting precipitate was filtered, washed with H2O (20 mL) then dried under high vacuum. The solid was then triturated with Et2O, and the resultant white solid was collected, to yield 36 mg of product. An extraction on the original filtrate was done using EtOAc (2×75 mL) and the combined organic layers were washed with brine (100 mL), dried over MgSO4, and concentrated in vacuo. The resulting off-white solid was subjected to flash chromatography on silica gel using 10% methanol:dichloromethane. Yield: 138 mg (79.5%); 1H NMR (300 MHz, DMSO-d6) δ 8.14 (s, 1H), 7.68 (s, 1H), 7.52-7.40 (m, 3H), 7.15-6.98 (m, 3H), 6.58 (s, 2H), 6.41 and 6.25 (2×s, 1H), 5.49 (s, 1H), 5.04 and 4.85 (2×s, 2H), 3.69 (s, 3H), 3.10 and 2.98 (2×s, 3H), 1.53 (s, 6H); ESI MS m/z 379 [C22H26N4O2+H]+

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. filtrationThe resulting precipitate was filtered
  3. washwashed with H2O (20 mL)
  4. customthen dried under high vacuum
  5. customThe solid was then triturated with Et2O
  6. customthe resultant white solid was collected

Sources & evidence

ORD record
ord-60eee2a79a504a13b82ee196c8747df1
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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