Pyridine → {4-[(Thiazole-2-carbonyl)-amino]-phenyl}-carbamic acid tert-butyl ester

HRID 1875321Notes

Reaction equation

HRID 1875321 reaction equation
[Si]([C:5]1[S:6][CH:7]=[CH:8][N:9]=1)(C)(C)C.[C:10](Cl)(Cl)=[O:11].C1(C)C=CC=CC=1.[C:21]([NH:28][C:29]1[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].N1C=CC=CC=1>C(Cl)Cl>[C:24]([O:23][C:21](=[O:22])[NH:28][C:29]1[CH:30]=[CH:31][C:32]([NH:35][C:10]([C:5]2[S:6][CH:7]=[CH:8][N:9]=2)=[O:11])=[CH:33][CH:34]=1)([CH3:27])([CH3:26])[CH3:25]

Participants

7

Reactant 5

HCID 1049PyridineHCID 1140TolueneHCID 6371PhosgeneHCID 5884532-TrimethylsilylthiazoleHCID 688611tert-Butyl (4-aminophenyl)carbamate

Product 1

HCID 57936351{4-[(Thiazole-2-carbonyl)-amino]-phenyl}-carbamic acid tert-butyl esterYield 10%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-TMS-thiazole (2.25 mL, 14.1 mmol) in DCM (5 mL) at 0° C. was slowly added a solution of phosgene in toluene (20%, 7.45 mL, 14.1 mmol) over 15 Min. After stirring for 2 h at RT, the resulting solution was slowly added via syringe to a solution of N-BOC-1,4-phenylenediamine (4.42 g, 21.2 mmol) and pyridine (2.3 mL, 28.2 mmol) in DCM (100 mL) at 0° C. After stirring for 20 h at RT, the reaction mixture was quenched by addition of sat. NaHCO3 (100 mL), EtOAc (150 mL) was added, and the phases were separated. The aqueous phase was extracted with EtOAc (2×75 mL), and the combined organic extracts were dried over MgSO4 and concentrated in vacuo. Purification by column chromatography (10-50% EtOAc in hexanes) afforded the product as an orange solid (452 mg, 10%). 1H-NMR (400 MHz, DMSO-d6) δ 10.66 (s, 1H), 9.34 (s, 1H), 8.12 (d, J=3.1 Hz, 1H), 8.09 (d, J=3.1 Hz, 1H), 7.72 (d, J=7.0 Hz, 2H), 7.42 (d, J=8.9 Hz, 2H), 1.48 (s, 9H). LC/MS (10-99%) M/Z: M+1 obs=320.3; tR=2.90 min.

Workup

  1. stirringAfter stirring for 20 h at RT
  2. customthe reaction mixture was quenched by addition of sat. NaHCO3 (100 mL), EtOAc (150 mL)
  3. additionwas added
  4. customthe phases were separated
  5. extractionThe aqueous phase was extracted with EtOAc (2×75 mL)
  6. dry with materialthe combined organic extracts were dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography (10-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a216789e212b4f2987c2c963b2cf632d
Source dataset
uspto-grants-2012_11
Patent number
US08309543B2

Reaction notes

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