1-Hydroxybenzotriazole → HCID 178503690, compound

HRID 1403131Notes

Reaction equation

HRID 1403131 reaction equation
[F:1][CH:2]([F:32])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([O:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]3)[CH:9]=2)[C:6]2[CH:28]=[CH:29][CH:30]=[CH:31][C:5]=2[N:4]=1.[C:33]([O:37][C:38]([N:40]([CH3:49])[C@H:41]([C:46](O)=[O:47])[CH2:42][CH2:43][S:44][CH3:45])=[O:39])([CH3:36])([CH3:35])[CH3:34].N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>O.CN(C)C=O>[F:32][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:11]=[C:10]([O:20][C@H:21]3[CH2:22][CH2:23][C@H:24]([NH:27][C:46](=[O:47])[C@@H:41]([N:40]([CH3:49])[C:38](=[O:39])[O:37][C:33]([CH3:34])([CH3:36])[CH3:35])[CH2:42][CH2:43][S:44][CH3:45])[CH2:25][CH2:26]3)[CH:9]=2)[C:6]2[CH:28]=[CH:29][CH:30]=[CH:31][C:5]=2[N:4]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11821461HCID 11821461, compoundHCID 178511706HCID 178511706, compound

Product 1

HCID 178503690HCID 178503690, compoundYield 79.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of trans-4-({6-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-2-(morpholin-4-yl)pyrimidin-4-yl}oxy)cyclohexanamine (700 mg) and N,N-dimethylformamide (7.0 mL) were added N-(tert-butoxycarbonyl)-N-methyl-L-methionine (622 mg), 1H-benzotriazol-1-ol (319 mg), and N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (452 mg), followed by stirring at room temperature overnight. After the completion of the reaction, water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate=90:10-40:60) to obtain tert-butyl [(2S)-1-{[trans-4-({6-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-2-(morpholin-4-yl)pyrimidin-4-yl}oxy)cyclohexyl]amino}-4-(methylsulfanyl)-1-oxobutan-2-yl]methylcarbamate (859 mg).

Workup

  1. additionwas added
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe desiccant was removed by filtration
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (hexane:ethyl acetate=90:10-40:60)

Sources & evidence

ORD record
ord-787a8b4cc76a4f2c97ab7279862157b3
Source dataset
uspto-grants-2014_12
Patent number
US08912180B2

Reaction notes

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