Hydrochloric Acid → HCID 86639687, compound

HRID 1426146Notes

Reaction equation

HRID 1426146 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH2:22][CH2:23][C:24](O)=[O:25])[CH:12]=[N:13][C:14]=1[NH:15][C:16]1[S:17][CH:18]=[C:19]([CH3:21])[N:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C([Cl:39])(=O)OCC.[CH3:40][N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1.[ClH:47]>C1COCC1>[ClH:39].[ClH:47].[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH2:22][CH2:23][C:24]([N:44]2[CH2:45][CH2:46][N:41]([CH3:40])[CH2:42][CH2:43]2)=[O:25])[CH:12]=[N:13][C:14]=1[NH:15][C:16]1[S:17][CH:18]=[C:19]([CH3:21])[N:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 531671-MethylpiperazineHCID 16661154HCID 16661154, compound

Product 1

HCID 86639687HCID 86639687, compoundYield 70.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 10 mL round-bottomed flask was charged with 3-(5-(benzyloxy)-6-(4-methylthiazol-2-ylamino)pyridin-3-yl)propanoic acid (60 mg, 0.16 mmol), triethylamine (0.091 ml, 0.65 mmol), and THF (3 mL). The reaction was cooled to 0° C., ethyl carbonochloridate (0.017 ml, 0.17 mmol) was added, and the reaction was stirred at 0° C. for 20 minutes. 1-Methylpiperazine (0.036 ml, 0.32 mmol) was added and stirred at 0° C. for 1.5 hours. The reaction was partitioned between EtOAc and water. The organic layer was dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified on a silica gel column (15% methanol in EtOAc with NH4OH) to afford the title compound (59.8 mg, 70.2% yield) as a white solid after HCl salt formation. 1H NMR (DMSO-d6) δ 11.25 (bs, 1H), 11.05 (bs, 1H), 7.89 (s, 1H), 7.62 (m, 3H), 7.45-7.33 (m, 3H), 6.83 (s, 1H), 5.32 (s, 2H), 4.43 (d, 1H), 4.06 (d, 1H), 3.47 (t, 1H), 3.38 (d, 2H), 3.01 (m, 2H), 2.84 (m, 3H), 2.74 (m, 5H), 2.32 (s, 3H). Mass spectrum (apci) m/z=452.2 (M+H-2HCl).

Workup

  1. stirringstirred at 0° C. for 1.5 hours
  2. customThe reaction was partitioned between EtOAc and water
  3. dry with materialThe organic layer was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a silica gel column (15% methanol in EtOAc with NH4OH)

Sources & evidence

ORD record
ord-42489a82489e426c87d213f741407cdf
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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