Ammonia → HCID 86639670, compound

HRID 1426120Notes

Reaction equation

HRID 1426120 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:27](CC)CC)C.C([Cl:37])(=O)OCC.N.CO>C1COCC1>[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]([NH2:27])=[O:24])[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

Participants

7

Reactant 5

HCID 222AmmoniaHCID 887MethanolHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 59225668HCID 59225668, compound

Product 1

HCID 86639670HCID 86639670, 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. 7M NH3 in methanol (2.186 mL, 15.31 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 then 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 hydrochloride (0.024 g, 33.01% yield). 1H NMR (DMSO-d6) δ 11.04 (bs, 1H), 7.97 (d, 1H), 7.59 (m, 4H), 7.42 (m, 2H), 7.36 (m, 1H), 7.17 (bs, 1H), 7.10 (m, 1H), 6.96 (s, 1H), 5.33 (s, 2H), 3.57 (s, 2H). Mass spectrum (apci) m/z=341.0 (M+H-HCl).

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-b9c7cf3e2ab343b0bef59b6a3810c578
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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