Acetic Acid → HCID 178444804, compound

HRID 1184639Notes

Reaction equation

HRID 1184639 reaction equation
C(O)(=O)C.C(O)(=O)C.[NH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]1[CH:42]=[CH:41][C:17]([O:18][CH2:19][CH2:20][N:21]([CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:22][C@H:23]([OH:34])[C@H:24]([C@H:26]2[C@H:31]([OH:32])[CH2:30][O:29][CH:28]([CH3:33])[O:27]2)[OH:25])=[CH:16][CH:15]=1.I.[NH2:44][C:45]1[C:46]([C:53]([NH:55][C:56](SC)=[NH:57])=[O:54])=[N:47][C:48]([Cl:52])=[C:49]([NH2:51])[N:50]=1.CCN(C(C)C)C(C)C>CCO>[NH2:44][C:45]1[C:46]([C:53]([NH:55][C:56](=[NH:57])[NH:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([O:18][CH2:19][CH2:20][N:21]([CH2:22][C@H:23]([OH:34])[C@@H:24]([OH:25])[C@H:26]3[C@H:31]([OH:32])[CH2:30][O:29][CH:28]([CH3:33])[O:27]3)[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])=[CH:41][CH:42]=2)=[O:54])=[N:47][C:48]([Cl:52])=[C:49]([NH2:51])[N:50]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 86689928HCID 86689928, compoundHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 178444804HCID 178444804, compoundYield 65.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

To a solution acetic acid salt 28 (189 mg, 0.313 mmol) and methyl 3,5-diamino-6-chloropyrazine-2-carbonylcarbamimidothioate hydroiodic acid salt (18, 192 mg, 0.502 mmol) in EtOH (8 mL) was added DIPEA (0.42 mL, 2.50 mmol) at room temperature. The reaction mixture was heated at 70° C. in a sealed tube for 2 h, then cooled to room temperature, and concentrated in vacuum. The residue was purified by column chromatography (silica gel, 9:1 CH2Cl2/MeOH, 80:18:2 CHCl3/MeOH/NH4OH) to afford carboxamide 20 (142 mg, 65%) as a yellow solid: 1H NMR (300 MHz, CD3OD) δ 7.10 (d, J=8.1 Hz, 2H), 6.84 (d, J=8.1 Hz, 2H), 4.66 (q, J=5.1 Hz, 1H), 4.06-4.01 (m, 3H), 3.94-3.89 (m, 1H), 3.82-3.74 (m, 2H), 3.49 (dd, J=9.3, 2.4 Hz, 1H), 2.96-2.78 (m, 3H), 2.67-2.61 (m, 5H), 1.68-1.67 (m, 4H), 1.50-1.48 (m, 2H), 1.29 (br s, 6H), 1.25 (d, J=5.1 Hz, 3H), 0.87 (t, J=6.9 Hz, 3H).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuum
  3. customThe residue was purified by column chromatography (silica gel, 9:1 CH2Cl2/MeOH, 80:18:2 CHCl3/MeOH/NH4OH)

Sources & evidence

ORD record
ord-a1dd21d65477432a8fbbc5e1bcf2e9ba
Source dataset
uspto-grants-2014_03
Patent number
US08669262B2

Reaction notes

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