1,4,5,6-Tetrahydropyrimidin-2-amine → (2S)-3-{4-[3-(1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl)-propoxy]-phenyl}-2-(toluene-4-sulfonylamino)-propionic acid tert-butyl ester

HRID 1250871Notes

Reaction equation

HRID 1250871 reaction equation
C([O:3][C:4](=O)[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C@@H:16]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[NH:17][S:18]([C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=2)(=[O:20])=[O:19])=[CH:11][CH:10]=1)C.[NH:36]1[CH2:41][CH2:40][CH2:39][N:38]=[C:37]1[NH2:42]>CN(C=O)C>[C:31]([O:30][C:28](=[O:29])[C@@H:16]([NH:17][S:18]([C:21]1[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=1)(=[O:19])=[O:20])[CH2:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][CH2:6][CH2:5][C:4](=[O:3])[NH:42][C:37]2[NH:38][CH2:39][CH2:40][CH2:41][N:36]=2)=[CH:10][CH:11]=1)([CH3:34])([CH3:33])[CH3:32]

Participants

4

Reactant 2

HCID 32874121,4,5,6-Tetrahydropyrimidin-2-amineHCID 699233804-{4-[(2S)-2-tert-Butoxycarbonyl-2-(toluene-4-sulfonylamino)-ethyl]-phenoxy}-butyric acid ethyl ester

Product 1

HCID 57120024(2S)-3-{4-[3-(1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl)-propoxy]-phenyl}-2-(toluene-4-sulfonylamino)-propionic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

295 mg of 4-{4-[(2S)-2-tert-Butoxycarbonyl-2-(toluene-4-sulfonylamino)-ethyl]-phenoxy}-butyric acid ethyl ester were dissolved in 15 ml of anhydrous DMF and 287 mg of 1,4,5,6-tetrahydropyrimidin-2-ylamine were added to the solution. The reaction mixture was stirred overnight at room temperature, and the solvent was removed in vacuo. The residue was dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution. The organic phase was dried with anhydrous magnesium sulfate, filtered and the solvent was removed in vacuo. The residue was chromatographed on silica gel eluting with a gradient of ethyl acetate/isopropanole/water (8/3/1 to 4/3/1). Yield 241 mg. MS: m/e=559.2 (M+H)+; 503.2.

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane
  3. washwashed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution
  4. dry with materialThe organic phase was dried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customThe residue was chromatographed on silica gel eluting with a gradient of ethyl acetate/isopropanole/water (8/3/1 to 4/3/1)

Sources & evidence

ORD record
ord-64de7d22af2a42c89823253f5ca076a7
Source dataset
uspto-grants-2002_01
Patent number
US06340679B1

Reaction notes

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