Methanol → Tetrahydro-pyran-4-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide

HRID 1060307Notes

Reaction equation

HRID 1060307 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:9][CH:8]=[C:7]([O:17][CH3:18])[C:5]=2[N:6]=1.C(N(C(C)C)C(C)C)C.[O:28]1[CH2:33][CH2:32][CH:31]([C:34](Cl)=[O:35])[CH2:30][CH2:29]1.CO>O1CCCC1>[CH3:18][O:17][C:7]1[C:5]2[N:6]=[C:2]([NH:1][C:34]([CH:31]3[CH2:32][CH2:33][O:28][CH2:29][CH2:30]3)=[O:35])[S:3][C:4]=2[C:10]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 2795505Oxane-4-carbonyl chlorideHCID 114028614-Methoxy-7-morpholinobenzo[d]thiazol-2-amine

Product 1

HCID 86584946Tetrahydro-pyran-4-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amideYield 94.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-amino-4-methoxy-7-morpholin-4-yl-benzothiazol (100 mg, 0.4 mmol) in tetrahydrofurane (2 ml) were subsequently added N-ethyl-diisopropylamine (194 □1, 1.1 mmol) and tetrahydropyran-4-carbonyl chloride (77 mg, 0.52 mmol, dissolved in 0.5 ml tetrahydrofurane) and the mixture refluxed for 3 h. The mixture was then cooled to 0° C., methanol (0.4 ml) was added and the mixture slowly warmed to 20° C. Then the mixture was evaporated to dryness, dichloromethane was added (3 ml) and extracted with saturated aqueous sodium carbonate. After back extraction of the aqueous phase with two portions of dichloromethane (3 ml), the combined organic phases were dryed with Na2SO4 and the solvent evaporated. The crude product was was then chromatographed over SiO2, eluting with CH2Cl2/MeOH 98:2, the product fractions were pooled and the solvent evaporated, to afford the title compound as a beige powder (142 mg, 76% yield), MS: m/e=378(M+H+).

Workup

  1. temperaturethe mixture refluxed for 3 h
  2. temperaturethe mixture slowly warmed to 20° C
  3. customThen the mixture was evaporated to dryness, dichloromethane
  4. additionwas added (3 ml)
  5. extractionextracted with saturated aqueous sodium carbonate
  6. extractionAfter back extraction of the aqueous phase with two portions of dichloromethane (3 ml)
  7. customthe solvent evaporated
  8. customThe crude product was was then chromatographed over SiO2
  9. washeluting with CH2Cl2/MeOH 98:2
  10. customthe solvent evaporated

Sources & evidence

ORD record
ord-e264128f0d9640a28687e1da6ecbcba2
Source dataset
uspto-grants-2003_02
Patent number
US06521754B2

Reaction notes

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