Ammonium Chloride → 2-{[(2-Methoxy-ethyl)-methyl-amino]-methyl}-3-methyl-3H-imidazole-4-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide

HRID 2222083Notes

Reaction equation

HRID 2222083 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH2:12])[S:11][C:7]=2[C:6]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:5][CH:4]=1.C([Li])(C)(C)C.C1([O:30][C:31]([C:33]2[N:34]([CH3:45])[C:35]([CH2:38][N:39]([CH2:41][CH2:42][O:43][CH3:44])[CH3:40])=[N:36][CH:37]=2)=O)C=CC=CC=1.[Cl-].[NH4+]>O1CCCC1.CCCCC.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH:12][C:31]([C:33]3[N:34]([CH3:45])[C:35]([CH2:38][N:39]([CH2:41][CH2:42][O:43][CH3:44])[CH3:40])=[N:36][CH:37]=3)=[O:30])[S:11][C:7]=2[C:6]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 114028614-Methoxy-7-morpholinobenzo[d]thiazol-2-amineHCID 585925902-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-3-methyl-3H-imidazole-4-carboxylic acid phenyl esterHCID 178418306HCID 178418306, compound

Product 1

HCID 116125822-{[(2-Methoxy-ethyl)-methyl-amino]-methyl}-3-methyl-3H-imidazole-4-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amideYield 31%

Reagents, catalysts & solvents 3

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-30 °C

Procedure

To a solution of 4-methoxy-7-morpholin-4-yl-benzothiazol-2-ylamine (220 mg, 0.83 mmol) in dry tetrahydrofurane (10 ml) at −70° C. is slowly added a solution of tert.butyllithium (1.1 ml of a 1.5 M solution in pentane corresponding to 1.65 mmol) and the remaining suspension slowly warmed to about −30° C. At this time, a solution of 2-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-3-methyl-3H-imidazole-4-carboxylic acid phenyl ester (252 mg, 0.83 mmol) in tetrahydrofurane (4 ml) was added and the mixture stirred for 1 h at room temperature. The reaction mixture was treated with saturated aqueous ammonium chloride solution (10 ml) followed by ethyl acetate (20 ml) and the formed precipitate collected. The phases were separated and the aqueous phase extracted three times with ethyl acetate. The combined organic layers were extracted twice with water, dried with magnesium sulfate and evaporated to dryness to yield another batch of raw product. Flash-chromatography on silica (eluent trichloromethane containing 30% of ethyl acetate) yielded the title compound as white solid (31% yield). MS: m/e=475(M+H+), mp 176-178° C.

Workup

  1. customthe formed precipitate collected
  2. customThe phases were separated
  3. extractionthe aqueous phase extracted three times with ethyl acetate
  4. extractionThe combined organic layers were extracted twice with water
  5. dry with materialdried with magnesium sulfate
  6. customevaporated to dryness
  7. customto yield another batch of raw product

Sources & evidence

ORD record
ord-5d55c12e1a4b47838f1a11d832a6239b
Source dataset
uspto-grants-2008_05
Patent number
US07371749B2

Reaction notes

Loading…