Sodium Bicarbonate → HCID 86679273, compound

HRID 1519707Notes

Reaction equation

HRID 1519707 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH:15]([C:17]1[CH:22]=[CH:21][C:20]([C:23]#[C:24][C:25]2[CH:50]=[CH:49][C:28]([C:29]([N:31]([CH3:48])[C@:32]([CH3:47])([C:37]([NH:39][O:40][CH:41]3[CH2:46][CH2:45][CH2:44][CH2:43][O:42]3)=[O:38])[C:33]([NH:35][CH3:36])=[O:34])=[O:30])=[CH:27][CH:26]=2)=[CH:19][CH:18]=1)=O.Cl.[F:52][CH2:53][CH2:54][O:55][CH:56]1[CH2:59][NH:58][CH2:57]1.C(=O)([O-])O.[Na+]>CN1C(=O)CCC1.C(OCC)(=O)C.O>[F:52][CH2:53][CH2:54][O:55][CH:56]1[CH2:59][N:58]([CH2:15][C:17]2[CH:18]=[CH:19][C:20]([C:23]#[C:24][C:25]3[CH:26]=[CH:27][C:28]([C:29]([N:31]([CH3:48])[C@:32]([CH3:47])([C:37]([NH:39][O:40][CH:41]4[CH2:46][CH2:45][CH2:44][CH2:43][O:42]4)=[O:38])[C:33]([NH:35][CH3:36])=[O:34])=[O:30])=[CH:49][CH:50]=3)=[CH:21][CH:22]=2)[CH2:57]1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 76847900HCID 76847900, compoundHCID 86679270(2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide

Product 1

HCID 86679273HCID 86679273, compoundYield 81%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Sodium triacetoxyborohydride (0.10 g) was added to a solution in NMP (1.5 mL) of (2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (0.15 g) as obtained in Example 16-(1) and 3-(2-fluoroethoxy)azetidine hydrochloride (63 mg) as obtained in Example 16-1-(2), under ice cooling in a nitrogen atmosphere. The mixture was stirred for 40 minutes at room temperature. Water and ethyl acetate were added, and the mixture was adjusted to pH 7.5 with a saturated aqueous solution of sodium hydrogen carbonate, whereafter the organic layer was isolated. The extract was washed with brine, and dried over anhydrous sodium sulfate. Then, the desiccant was filtered out, and the solvent was distilled off under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/acetone=80/20→50/50) to obtain (2S)-2-[{4-[(4-{[3-(2-fluoroethoxy)azetidin-1-yl]methyl}phenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (yellow oil) (0.14 g, 81%).

Workup

  1. customas obtained in Example 16-1-(2), under ice cooling in a nitrogen atmosphere
  2. customwas isolated
  3. washThe extract was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThen, the desiccant was filtered out
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/acetone=80/20→50/50)

Sources & evidence

ORD record
ord-177d3f4d07e44c329c5dc317a601b186
Source dataset
uspto-grants-2015_07
Patent number
US09073821B2

Reaction notes

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