HCID 25241964, compound → HCID 59718955, compound

HRID 1852538Notes

Reaction equation

HRID 1852538 reaction equation
[CH3:1][O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]([NH2:11])[CH2:7][CH2:6]1)=[O:4].Cl[C:13]1[N:18]=[C:17]([N:19]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]=[N:20]2)[C:16]([Cl:28])=[CH:15][N:14]=1>C1COCC1>[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH:8]([NH:11][C:13]2[N:18]=[C:17]([N:19]3[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=4[N:21]=[N:20]3)[C:16]([Cl:28])=[CH:15][N:14]=2)[CH2:7][CH2:6]1)=[O:4]

Participants

4

Reactant 2

HCID 25241964HCID 25241964, compoundHCID 178501207HCID 178501207, compound

Product 1

HCID 59718955HCID 59718955, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

trans-4-Amino-cyclohexanecarboxylic acid methyl ester (727 mg, 3.76 mmol) was added in portions, at RT under nitrogen atmosphere, to a solution of 1-(2,5-dichloro-pyrimidin-4-yl)-1H-benzotriazole (500 mg, 1.88 mmol) in THF (50 mL) followed by TEA (0.79 mL, 5.64 mmol). The resultant white suspension was stirred at RT overnight, and then at 60° C. for 2.5 days. The mixture was partitioned between water (100 mL) and EtOAc (100 mL). The organic layer was separated, washed twice with water (100 mL) and once with brine (100 mL), then dried over Na2SO4, filtered and the solvent evaporated under reduced pressure to give an off-white solid. This crude material was purified via flash chromatography (toluene/EtOAc, 90/10) to afford 538 mg (74% yield) of 4-(4-benzotriazol-1-yl-5-chloro-pyrimidin-2-ylamino)-cyclohexanecarboxylic acid methyl ester as an off-white solid. MS: 387.10 (M+1)+, 359.13 ((M+1)+−28).

Workup

  1. waitat 60° C. for 2.5 days
  2. customThe mixture was partitioned between water (100 mL) and EtOAc (100 mL)
  3. customThe organic layer was separated
  4. washwashed twice with water (100 mL) and once with brine (100 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customthe solvent evaporated under reduced pressure
  8. customto give an off-white solid
  9. customThis crude material was purified via flash chromatography (toluene/EtOAc, 90/10)

Sources & evidence

ORD record
ord-ab888a1219c049b4b8426627c9d069f6
Source dataset
uspto-grants-2015_02
Patent number
US08962622B2

Reaction notes

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