Triethylamine → HCID 86639669, compound

HRID 1426119Notes

Reaction equation

HRID 1426119 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([NH:15][C:16]2[S:17][CH:18]=[C:19]([CH2:21][C:22]([OH:24])=O)[N:20]=2)=[N:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C([Cl:37])(=O)OCC.[CH3:38][N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1>C1COCC1>[ClH:37].[ClH:37].[CH2:1]([O:8][C:9]1[C:10]([NH:15][C:16]2[S:17][CH:18]=[C:19]([CH2:21][C:22]([N:42]3[CH2:43][CH2:44][N:39]([CH3:38])[CH2:40][CH2:41]3)=[O:24])[N:20]=2)=[N:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 531671-MethylpiperazineHCID 59225668HCID 59225668, compound

Product 1

HCID 86639669HCID 86639669, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-5 °C

Procedure

A 100 mL round-bottomed flask was charged with 2-(2-(3-(benzyloxy)pyridin-2-ylamino)thiazol-4-yl)acetic acid (prepared according to Example 24; 0.050 g, 0.1465 mmol) and THF (30 mL) and cooled to −5° C. Triethylamine (0.03112 g, 0.3076 mmol) and ethyl carbonochloridate (0.07002 mL, 0.7323 mmol) were added successively, and the reaction mixture was stirred at −5° C. for 30 minutes. 1-Methylpiperazine (0.07335 g, 0.7323 mmol) was added, and the reaction mixture was stirred at −5° C. for 30 minutes and then at room temperature for 1 hour. The reaction mixture was washed with water, the organic layer was separated, dried and concentrated, and the residue was purified first by silica gel chromatography and then by reverse phase chromatography to give the title compound as the free base. The free base was dissolved in dichloromethane, and 2M HCl in ether was added. The mixture was concentrated to provide 2-(2-(3-(benzyloxy)pyridin-2-ylamino)thiazol-4-yl)-1-(4-methylpiperazin-1-yl)ethanone dihydrochloride (0.024 g, 33.01% yield). 1H NMR (DMSO-d6) δ 10.35 (bs, 1H), 10.11 (bs, 1H), 7.89 (dd, 1H), 7.57 (m, 2H), 7.42 (m, 3H), 7.35 (m, 1H), 6.95 (m, 1H), 6.81 (s, 1H), 5.28 (s, 2H), 4.45 (m, 1H), 4.21 (m, 1H), 3.79 (s, 2H), 3.41 (m, 3H), 2.98 (m, 3H), 2.78 (d, 3H). Mass spectrum (apci) m/z=424.2 (M+H-2HCl).

Workup

  1. stirringthe reaction mixture was stirred at −5° C. for 30 minutes
  2. waitat room temperature for 1 hour
  3. washThe reaction mixture was washed with water
  4. customthe organic layer was separated
  5. customdried
  6. concentrationconcentrated
  7. customthe residue was purified first by silica gel chromatography

Sources & evidence

ORD record
ord-138d32f58b5b4d60ab9123356dc18f3e
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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