Phosphorus trichloride → HCID 20145088, compound

HRID 1906010Notes

Reaction equation

HRID 1906010 reaction equation
[N:1]1([CH2:6][C:7]2[CH:8]=[C:9]([CH:15]=[CH:16][CH:17]=2)[O:10][CH2:11][CH2:12][CH2:13][NH2:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.P(Cl)(Cl)[Cl:19].[NH2:22][C:23]1[S:24][C:25]([C:31]2[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=2)=[C:26]([C:28](O)=[O:29])[N:27]=1>N1C=CC=CC=1>[ClH:19].[NH2:22][C:23]1[S:24][C:25]([C:31]2[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=2)=[C:26]([C:28](=[O:29])[NH:14][CH2:13][CH2:12][CH2:11][O:10][C:9]2[CH:15]=[CH:16][CH:17]=[C:7]([CH2:6][N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[CH:8]=2)[N:27]=1

Participants

5

Reactant 3

HCID 24387Phosphorus trichlorideHCID 127974543-{3-[(Pyrrolidin-1-yl)methyl]phenoxy}propan-1-amineHCID 201449862-Amino-5-(pyridin-4-yl)-1,3-thiazole-4-carboxylic acid

Product 1

HCID 20145088HCID 20145088, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 3-[3-(pyrrolidin-1-ylmethyl)phenoxy]propylamine (2.33 g) and phosphorus trichloride (0.44 ml) in pyridine (20 ml) was added 2-amino-5-(4-pyridyl)-4-thiazolecarboxylic acid (1.1 g) and the mixture was stirred at 80° C. for 3 hours. The reaction mixture was evaporated in vacuo and the residue was dissolved in a mixture of ethyl acetate and water. The resultant mixture was adjusted to pH 1.0 with 10% hydrochloric acid. The separated aqueous layer was adjusted to pH 8 with saturated potassium carbonate and extracted with chloroform. The solvent was dried over magnesium sulfate and evaporated in vacuo. The residue was subjected to column chromatography on alumina eluting with a mixture of ethyl acetate and tetrahydrofuran (3:7). The fractions containing the desired compound were combined and evaporated in vacuo. To the oily residue was added a solution of ethyl acetate and hydrochloric acid. The precipitate was collected by filtration and dried over phosphorus pentoxide in vacuo to afford 2-amino-5-(4-pyridyl)-4-[ 3-[3-(pyrrolidin-1-yl-methyl)phenoxy]propylcarbamoyl]thiazole hydrochloride (0.34 g).

Workup

  1. customThe reaction mixture was evaporated in vacuo
  2. dissolutionthe residue was dissolved in a mixture of ethyl acetate and water
  3. extractionextracted with chloroform
  4. dry with materialThe solvent was dried over magnesium sulfate
  5. customevaporated in vacuo
  6. additionThe residue was subjected to column chromatography on alumina eluting with a mixture of ethyl acetate and tetrahydrofuran (3:7)
  7. additionThe fractions containing the desired compound
  8. customevaporated in vacuo
  9. additionTo the oily residue was added a solution of ethyl acetate and hydrochloric acid
  10. filtrationThe precipitate was collected by filtration
  11. dry with materialdried over phosphorus pentoxide in vacuo

Sources & evidence

ORD record
ord-ad73fd4553f44205bd840ab31db40ee9
Source dataset
uspto-grants-1987_03
Patent number
US04649146

Reaction notes

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