Phosphorus trichloride → HCID 20145088, compound

HRID 648591Notes

Reaction equation

HRID 648591 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

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 stired 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-f40f8fa7cf214c39a28cd0ddc8180641
Source dataset
uspto-grants-1988_04
Patent number
US04735957

Reaction notes

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