Sodium Carbonate → (S)-tert-butyl (1-((5-(2-chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate

HRID 2284774Notes

Reaction equation

HRID 2284774 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:13])=[N:11][CH:12]=1.[C:18]([N:25]([CH3:31])[C@H:26]([C:28](O)=[O:29])[CH3:27])([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].Cl.C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C(OCC)(=O)C>[Cl:13][C:10]1[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:29])[C@@H:26]([N:25]([CH3:31])[C:18](=[O:19])[O:20][C:21]([CH3:22])([CH3:24])[CH3:23])[CH3:27])=[CH:12][N:11]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 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 90052304(S)-tert-butyl (1-((5-(2-chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamateYield 113.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-(5-amino-1-pentyn-1-yl)-2-chloro-N-propylpyrimidin-4-amine (K2, 505 mg) and N-Boc-N-methyl-L-alanine (270 mg) in N,N-dimethylformamide (5 mL), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (635 mg) and N,N-diisopropylethylamine (378 μL) were added at room temperature, and the mixture was stirred overnight at the same temperature. To the reaction mixture, saturated aqueous sodium carbonate and ethyl acetate were added. The organic layer was separated, washed with water, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (eluent, 50% hexane/50% ethyl acetate) to obtain (S)-tert-butyl (1-((5-(2-chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate (L1, 660 mg).

Workup

  1. customThe organic layer was separated
  2. washwashed with water
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by basic silica gel column chromatography (eluent, 50% hexane/50% ethyl acetate)

Sources & evidence

ORD record
ord-f9d88be0d8bf486b84af3da3c1e8571e
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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