Triethylamine → HCID 86605987, compound

HRID 217942Notes

Reaction equation

HRID 217942 reaction equation
I.[NH2:2][C:3]1[C:4]([C:11]([NH:13][C:14](=[NH:17])SC)=[O:12])=[N:5][C:6]([Cl:10])=[C:7]([NH2:9])[N:8]=1.C([N:20](CC)CC)C.Cl.N[CH2:27][CH2:28][CH2:29][CH2:30][C:31]1[CH:42]=[CH:41][C:34]([C:35]([NH:37][CH2:38][CH2:39][OH:40])=[O:36])=[CH:33][CH:32]=1>C1COCC1.CO>[ClH:10].[NH2:2][C:3]1[C:4]([C:11]([N:13]([CH2:27][CH2:28][CH2:29][CH2:30][C:31]2[CH:42]=[CH:41][C:34]([C:35]([NH:37][CH2:38][CH2:39][OH:40])=[O:36])=[CH:33][CH:32]=2)[C:14]([NH2:17])=[NH:20])=[O:12])=[N:5][C:6]([Cl:10])=[C:7]([NH2:9])[N:8]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 673681504-(4-Aminobutyl)-N-(2-hydroxyethyl)benzamide hydrochlorideHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 86605987HCID 86605987, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

1-(3,5-Diamino-6-chloropyrazinoyl)-2-methylisothiourea hydriodide (0.48 g, 1.24 mmol) and triethylamine (0.7 mL, 4.74 mmol) were sequentially added into a solution of 28 (0.28 g, 1.19 mmol) in a mixture of THF/MeOH (4 mL, 1/1). The reaction mixture was stirred in the boiling solvent for 4 h, then at room temperature overnight. The solvent was evaporated. The free base of the target compound 29 (0.36 g, 62%) was purified by Flash™ (BIOTAGE, Inc) (90 g silica gel cartridge 40M, 12:1:0.1 chloroform/ethanol/concentrated ammonium hydroxide) as a yellow solid. 100 mg of the yellow solid was treated with 2 mL of 3% HCl. The precipitate was collected by filtration, washed with water (2×5 mL) and dried under vacuum to give 85 mg (79%) of 29 as a yellow powder. 1H NMR (300 MHz, DMSO-d6) δ 1.60 (m, 4H), 2.68 (m, 2H), 3.28 (m, 4H), 3.49 (m, 2H), 4.80 (m, 1H), 7.28 (d, 2H), 7.44 (br s, 2H), 7.82 (d, 2H), 8.45 (m, 1H). m/z (APCI)=449 [C19H25ClN8O3+H]+.

Workup

  1. customat room temperature
  2. customovernight
  3. customThe solvent was evaporated
  4. customThe free base of the target compound 29 (0.36 g, 62%) was purified by Flash™ (BIOTAGE, Inc) (90 g silica gel cartridge 40M, 12:1:0.1 chloroform/ethanol/concentrated ammonium hydroxide) as a yellow solid
  5. addition100 mg of the yellow solid was treated with 2 mL of 3% HCl
  6. filtrationThe precipitate was collected by filtration
  7. washwashed with water (2×5 mL)
  8. customdried under vacuum

Sources & evidence

ORD record
ord-9f6fc6d8d8884320b454da1dcdd44b63
Source dataset
uspto-grants-2012_06
Patent number
US08198286B2

Reaction notes

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