Triethylamine → Pyrimidine-5-carboxylic acid{1-[2-chloro-4-(2-chloro-phenoxy)-benzyl-carbamoyl]-cyclopropyl}-amide

HRID 1406351Notes

Reaction equation

HRID 1406351 reaction equation
C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[Cl:30][C:31]1[CH:38]=[C:37]([O:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[Cl:46])[CH:36]=[CH:35][C:32]=1[CH2:33][NH2:34].[N:47]1[CH:52]=[C:51]([C:53]([NH:55][C:56]2([C:59](O)=[O:60])[CH2:58][CH2:57]2)=[O:54])[CH:50]=[N:49][CH:48]=1>O1CCCC1.CN(C=O)C>[Cl:30][C:31]1[CH:38]=[C:37]([O:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[Cl:46])[CH:36]=[CH:35][C:32]=1[CH2:33][NH:34][C:59]([C:56]1([NH:55][C:53]([C:51]2[CH:50]=[N:49][CH:48]=[N:47][CH:52]=2)=[O:54])[CH2:58][CH2:57]1)=[O:60]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 584879012-Chloro-4-(2-chloro-phenoxy)-benzylamineHCID 594962911-[(Pyrimidine-5-carbonyl)-amino]cyclopropanecarboxylic acid

Product 1

HCID 58487801Pyrimidine-5-carboxylic acid{1-[2-chloro-4-(2-chloro-phenoxy)-benzyl-carbamoyl]-cyclopropyl}-amideYield 29%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

85 mg (0.84 mmol) of triethylamine, 130 mg (0.40 mmol) of TBTU and 100 mg (0.37 mmol) of 2-chloro-4-(2-chloro-phenoxy)-benzylamine were added to a solution of 80 mg (0.38 mmol) of 1-[(pyrimidin-5-carbonyl)-amino]-cyclopropanecarboxylic acid (from 1 b) in 30 mL tetrahydrofuran and 5 mL DMF and the mixture was stirred overnight at ambient temperature. Then the mixture was evaporated to dryness and the residue was combined with 2 M potassium carbonate solution. It was extracted with ethyl acetate and the organic phase was washed with water and saturated sodium chloride solution, dried and evaporated down. The crude product thus obtained was purified by reversed-phase chromatography. The fractions were evaporated down to the aqueous phase, made basic with ammonia and extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried and evaporated down. The residue was evaporated out with ether and dried.

Workup

  1. customThen the mixture was evaporated to dryness
  2. extractionIt was extracted with ethyl acetate
  3. washthe organic phase was washed with water and saturated sodium chloride solution
  4. customdried
  5. customevaporated down

Sources & evidence

ORD record
ord-68fbdd75702b48309474722479d9365a
Source dataset
uspto-grants-2014_12
Patent number
US08916589B2

Reaction notes

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