1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → tert-butyl (4-(4-((1-methyl-3-(2-oxoimidazolidin-1-yl)-1H-pyrazol-4-yl)carbamoyl)-1,3-oxazol-2-yl)pyridin-2-yl)(2,2,2-trifluoroethyl)carbamate

HRID 632813Notes

Reaction equation

HRID 632813 reaction equation
Cl.[NH2:2][C:3]1[C:4]([N:9]2[CH2:13][CH2:12]C(C)(C)[C:10]2=[O:16])=[N:5][N:6]([CH3:8])[CH:7]=1.[C:17]([O:21][C:22]([N:24]([CH2:39][C:40]([F:43])([F:42])[F:41])[C:25]1[CH:30]=[C:29]([C:31]2[O:32][CH:33]=[C:34]([C:36](O)=[O:37])[N:35]=2)[CH:28]=[CH:27][N:26]=1)=[O:23])([CH3:20])([CH3:19])[CH3:18].Cl.C[N:46](C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>CC(N(C)C)=O.O.C(N(CC)CC)C>[CH3:8][N:6]1[CH:7]=[C:3]([NH:2][C:36]([C:34]2[N:35]=[C:31]([C:29]3[CH:28]=[CH:27][N:26]=[C:25]([N:24]([CH2:39][C:40]([F:43])([F:42])[F:41])[C:22](=[O:23])[O:21][C:17]([CH3:20])([CH3:19])[CH3:18])[CH:30]=3)[O:32][CH:33]=2)=[O:37])[C:4]([N:9]2[CH2:13][CH2:12][NH:46][C:10]2=[O:16])=[N:5]1

Participants

8

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 1180609051-(4-amino-1-methyl-1H-pyrazol-3-yl)-3,3-dimethylpyrrolidin-2-one hydrochlorideHCID 1180609712-(2-((Tert-butoxycarbonyl)(2,2,2-trifluoroethyl)amino)pyridin-4-yl)oxazole-4-carboxylic acid

Product 1

HCID 131735465tert-butyl (4-(4-((1-methyl-3-(2-oxoimidazolidin-1-yl)-1H-pyrazol-4-yl)carbamoyl)-1,3-oxazol-2-yl)pyridin-2-yl)(2,2,2-trifluoroethyl)carbamateYield 64.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8471TriethylamineSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 1-(4-amino-1-methyl-1H-pyrazol-3-yl)-3,3-dimethylpyrrolidin-2-one hydrochloride (3.09 g), 2-(2-((tert-butoxycarbonyl)(2,2,2-trifluoroethyl)amino)pyridin-4-yl)-1,3-oxazole-4-carboxylic acid (5.50 g), N-(3-(dimethylamino)propyl)-N′-ethylcarbodiimide hydrochloride (3.27 g) and 1-hydroxybenzotriazole hydrate (2.39 g) in DMA (40 mL) was added triethylamine (3.96 mL), and the mixture was stirred at room temperature for 1 hr, and then at 50° C. for 3 hr. The reaction mixture was ice-cooled, and water was added thereto. The precipitate was collected by filtration, and washed successively with DMA/water (1/2), water and diisopropyl ether. The obtained solid was suspended in ethanol, and the suspension was stirred at room temperature for 15 min, and the solid was collected by filtration, and washed with ethanol to give the title compound (4.46 g).

Workup

  1. waitat 50° C. for 3 hr
  2. temperaturecooled
  3. filtrationThe precipitate was collected by filtration
  4. washwashed successively with DMA/water (1/2), water and diisopropyl ether
  5. stirringthe suspension was stirred at room temperature for 15 min
  6. filtrationthe solid was collected by filtration
  7. washwashed with ethanol

Sources & evidence

ORD record
ord-30f31b8fb76243a684ffc1d54cb20fe5
Source dataset
uspto-grants-2016_04
Patent number
US09321757B2

Reaction notes

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