1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 90052287, compound

HRID 2284751Notes

Reaction equation

HRID 2284751 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[C:8]([N:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)=[N:9][C:10]([NH:13][C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][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:18]([C:17]1[CH:20]=[CH:21][C:14]([NH:13][C:10]2[N:9]=[C:8]([N:22]3[CH2:23][CH2:24][CH2:25][CH2:26]3)[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:15][CH:16]=1)#[N:19]

Participants

7

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 90052286HCID 90052286, compound

Product 1

HCID 90052287HCID 90052287, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Procedure

To a solution of 4-((5-(5-amino-1-pentyn-1-yl)-4-(pyrrolidin-1-yl)pyrimidin-2-yl)amino)benzonitrile (H4, 2.64 g), N-Boc-N-methyl-L-alanine (3.10 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.92 g) and 1-hydroxybenzotriazole monohydrate (2.06 g) in N,N-dimethylformamide (40 mL), N,N-diisopropylethylamine (3.98 mL) was added at room temperature, and the mixture was stirred at the same temperature for 3 hours. The solvent was evaporated under reduced pressure, and to the obtained residue, saturated aqueous sodium hydrogencarbonate and ethyl acetate were added. The organic layer was separated, washed successively with saturated aqueous sodium hydrogencarbonate 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, 30 to 5% hexane in ethyl acetate). The obtained solid matter was washed with a mixed solvent of ethyl acetate and hexane, and then dried under reduced pressure to obtain (S)-tert-butyl (1 -((5-(2-((4-cyanophenyl)amino)-4-(pyrrolidin-1-yl)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate (H5, 2.39 g) as white solid.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. additionto the obtained residue, saturated aqueous sodium hydrogencarbonate and ethyl acetate were added
  3. customThe organic layer was separated
  4. washwashed successively with saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (eluent, 30 to 5% hexane in ethyl acetate)
  8. washThe obtained solid matter was washed with a mixed solvent of ethyl acetate and hexane
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-8fe475453e5440929fc34aa103343a1d
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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