Water → tert-butyl methyl(2-(methyl((3-(3-(3-methylbut-2-enamido)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)amino)ethyl)carbamate

HRID 570786Notes

Reaction equation

HRID 570786 reaction equation
C([C:3]1[C:4]([C:14]2[CH:15]=[C:16]([NH:20][C:21](=[O:26])[CH:22]=[C:23]([CH3:25])[CH3:24])[CH:17]=[CH:18][CH:19]=2)=[N:5][N:6]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][O:9]2)[CH:7]=1)=O.[CH3:27][N:28]([CH2:36][CH2:37][NH:38][CH3:39])[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32].[BH3-][C:41]#N.[Na+].O>CO.[Cl-].[Cl-].[Zn+2]>[CH3:27][N:28]([CH2:36][CH2:37][N:38]([CH3:41])[CH2:39][C:3]1[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([NH:20][C:21](=[O:26])[CH:22]=[C:23]([CH3:25])[CH3:24])[CH:15]=2)=[N:5][N:6]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][O:9]2)[CH:7]=1)[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32]

Participants

7

Reactant 4

HCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 14403871tert-Butyl methyl(2-(methylamino)ethyl)carbamateHCID 90425471N-(3-(4-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)phenyl)-3-methylbut-2-enamide

Product 1

HCID 117617465tert-butyl methyl(2-(methyl((3-(3-(3-methylbut-2-enamido)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)amino)ethyl)carbamateYield 47%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Procedure

To a solution of N-(3-(4-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)phenyl)-3-methylbut-2-enamide (0.210 g, 0.00062 mol) in methanol (4 mL) were added TEA (313 mg, 0.0031 mol), ZnCl2 (0.008 g, 0.000062 mol) and tert-butyl methyl(2(methylamino)ethyl)carbamate (0.138 g, 0.00074 mol). The reaction mixture was stirred at rt for 45 min. NaCNBH3 (0.580 g, 0.00913 mol) was added and stirred for 2 h at rt. The reaction was poured into water (100 mL) and extracted with EtOAc (100 mL×2). The combined extracts was washed with brine (200 mL), dried over sodium sulphate and concentrated under vacuum. The residue was purified by SGC using DCM:MeOH (0%-4%) as eluent to obtain tert-butyl methyl(2-(methyl((3-(3-(3-methylbut-2-enamido)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)amino)ethyl)carbamate (0.150 g, Yield: 47%). LCMS (ESI): RT=2.03 min, m/z=526.5 [M+H]+.

Workup

  1. stirringstirred for 2 h at rt
  2. extractionextracted with EtOAc (100 mL×2)
  3. washThe combined extracts was washed with brine (200 mL)
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by SGC

Sources & evidence

ORD record
ord-73ffed1a8b99435f81da6e49dbe98276
Source dataset
uspto-grants-2015_05
Patent number
US09023883B2

Reaction notes

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