1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (S)-tert-butyl (1-((5-(2-((3-fluorophenyl)amino)-4-((3-methoxypropyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate

HRID 2284760Notes

Reaction equation

HRID 2284760 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[C:8]([NH:21][CH2:22][CH2:23][CH2:24][O:25][CH3:26])=[N:9][C:10]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[N:11][CH:12]=1.[C:27]([N:34]([CH3:40])[C@H:35]([C:37](O)=[O:38])[CH3:36])([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(N(CC)C(C)C)(C)C.C(OCC)(=O)C.O>[F:20][C:16]1[CH:15]=[C:14]([NH:13][C:10]2[N:9]=[C:8]([NH:21][CH2:22][CH2:23][CH2:24][O:25][CH3:26])[C:7]([C:6]#[C:5][CH2:4][CH2:3][CH2:2][NH:1][C:37](=[O:38])[C@@H:35]([N:34]([CH3:40])[C:27](=[O:28])[O:29][C:30]([CH3:31])([CH3:33])[CH3:32])[CH3:36])=[CH:12][N:11]=2)[CH:19]=[CH:18][CH:17]=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 900521525-(5-amino-1-pentyn-1-yl)-N2-(3-fluorophenyl)-N4-(3-methoxypropyl)pyrimidine-2,4-diamine

Product 1

HCID 90052150(S)-tert-butyl (1-((5-(2-((3-fluorophenyl)amino)-4-((3-methoxypropyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 81531DiisopropylethylamineSolvent

Procedure

To a solution of 5-(5-amino-1-pentyn-1-yl)-N2-(3-fluorophenyl)-N4-(3-methoxypropyl)pyrimidine-2,4-diamine (J7, 55 mg), N-Boc-N-methyl-L-alanine (63 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (59 mg) and 1-hydroxybenzotriazole monohydrate (42 mg) in N,N-dimethylformamide (700 μL), N,N-diisopropylethylamine (108 μL) was added at room temperature, and the mixture was stirred at the same temperature for 3 hours. To the reaction mixture, water and ethyl acetate were added. The organic layer was separated, 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 to obtain (S)-tert-butyl (1-((5-(2-((3-fluorophenyl)amino)-4-((3-methoxypropyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate (J8, 84 mg).

Workup

  1. customThe organic layer was separated
  2. washwashed successively with water and saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5791b862a45b462cb79e48a65b3e48e5
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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