1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (S)-tert-butyl (1-((5-(2-((1H-benzo[d][1,2,3]triazol-1-yl)oxy)-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate

HRID 2284772Notes

Reaction equation

HRID 2284772 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[C:8]([NH:14][CH2:15][CH2:16][CH3:17])=[N:9][C:10](Cl)=[N:11][CH:12]=1.[C:18]([N:25]([CH3:31])[C@H:26]([C:28]([OH:30])=O)[CH3:27])([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].Cl.C(N=C=NCCCN(C)C)C.O.[OH:45][N:46]1[C:50]2[CH:51]=[CH:52][CH:53]=[CH:54][C:49]=2[N:48]=[N:47]1>CN(C)C=O.C(N(CC)C(C)C)(C)C.C(OCC)(=O)C.O>[N:46]1([O:45][C:10]2[N:9]=[C:8]([NH:14][CH2:15][CH2:16][CH3:17])[C:7]([C:6]#[C:5][CH2:4][CH2:3][CH2:2][NH:1][C:28](=[O:30])[C@@H:26]([N:25]([CH3:31])[C:18](=[O:19])[O:20][C:21]([CH3:22])([CH3:23])[CH3:24])[CH3:27])=[CH:12][N:11]=2)[C:50]2[CH:51]=[CH:52][CH:53]=[CH:54][C:49]=2[N:48]=[N:47]1

Participants

9

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 900521545-(5-amino-1-pentyn-1-yl)-2-chloro-N-propylpyrimidin-4-amine

Product 1

HCID 90052416(S)-tert-butyl (1-((5-(2-((1H-benzo[d][1,2,3]triazol-1-yl)oxy)-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamateYield 35.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 81531DiisopropylethylamineSolvent

Procedure

To a solution of 5-(5-amino-1-pentyn-1-yl)-2-chloro-N-propylpyrimidin-4-amine (K2, 510 mg), N-Boc-N-methyl-L-alanine (493 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.16 g) and 1-hydroxybenzotriazole monohydrate (930 mg) in N,N-dimethylformamide (10 mL), N,N-diisopropylethylamine (690 μL) was added at room temperature, and the mixture was stirred at the same temperature for 12 hours. To the reaction mixture, water and ethyl acetate were added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, washed successively with water and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 70 to 40% hexane in ethyl acetate) to obtain (S)-tert-butyl (1-((5-(2-((1H-benzo[d][1,2,3]triazol-1-yl)oxy)-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate (K3, 380 mg).

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washwashed successively with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent, 70 to 40% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-cd05bd0e92bc4c7f90091c5117164106
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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