Tributylamine → (2S)-N,2-dimethyl-2-{methyl[(4-{(E)-2-[4-(morpholin-4-ylmethyl)phenyl]ethenyl}phenyl)carbonyl]amino}-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide

HRID 1519739Notes

Reaction equation

HRID 1519739 reaction equation
CC1C=CC(P([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)C2C=CC(C)=CC=2)=CC=1.[CH2:23](N(CCCC)CCCC)[CH2:24]CC.I[C:37]1[CH:62]=[CH:61][C:40]([C:41]([N:43]([CH3:60])[C@:44]([CH3:59])([C:49]([NH:51][O:52][CH:53]2[CH2:58][CH2:57][CH2:56][CH2:55][O:54]2)=[O:50])[C:45]([NH:47][CH3:48])=[O:46])=[O:42])=[CH:39][CH:38]=1.C(C1C=CC(C=O)=CC=1)=C.[NH:73]1[CH2:78][CH2:77][O:76][CH2:75][CH2:74]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)(Cl)Cl.C(O)(=O)C.CN(C=O)C>[CH3:48][NH:47][C:45](=[O:46])[C@:44]([CH3:59])([N:43]([CH3:60])[C:41]([C:40]1[CH:61]=[CH:62][C:37](/[CH:23]=[CH:24]/[C:16]2[CH:17]=[CH:18][C:19]([CH2:22][N:73]3[CH2:78][CH2:77][O:76][CH2:75][CH2:74]3)=[CH:20][CH:21]=2)=[CH:38][CH:39]=1)=[O:42])[C:49]([NH:51][O:52][CH:53]1[CH2:58][CH2:57][CH2:56][CH2:55][O:54]1)=[O:50]

Participants

12

Reactant 7

HCID 7622TributylamineHCID 8083MorpholineHCID 13956Phosphine, tris(4-methylphenyl)-HCID 393894-VinylbenzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 86679252HCID 86679252, compound2×

Product 1

HCID 86679298(2S)-N,2-dimethyl-2-{methyl[(4-{(E)-2-[4-(morpholin-4-ylmethyl)phenyl]ethenyl}phenyl)carbonyl]amino}-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamideYield 31%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 176Acetic AcidSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Palladium acetate (12 mg), tris(4-methylphenyl)phosphine (24 mg), tri-n-butylamine (0.25 mL) were added to a DMF (1.2 ml) solution of (2S)-2-[(4-iodobenzoyl)(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (Intermediate 15, 90 mg) and 4-ethenylbenzaldehyde (98 mg) obtained by the same method as the synthesis method described in the literature (Journal of Electroanalytical Chemistry, 2002, Vol. 529(1), pp. 43-50), and the mixture was stirred overnight at 80° C. The solvent was distilled off under reduced pressure, and the resulting residue was purified by OH type silica gel chromatography (gradient elution with chloroform/methanol=100/0→94/6) to obtain a crude product. Morpholine (30 μl) and acetic acid (20 μl) were added to a chloroform (1.0 ml) solution of the resulting crude product, and the mixture was stirred for 2.5 hours at room temperature. Further, sodium triacetoxyborohydride (62 mg) was added, and the mixture was stirred overnight at room temperature. A saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, the mixture was extracted with chloroform, and the organic layer was concentrated under reduced pressure. The resulting residue was purified by NH type silica gel chromatography (gradient elution with chloroform/methanol=100/0→94/6) to obtain (2S)-N,2-dimethyl-2-{methyl[(4-{(E)-2-[4-(morpholin-4-ylmethyl)phenyl]ethenyl}phenyl)carbonyl]amino}-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (colorless oil) (32 mg, 31%).

Workup

  1. customobtained by the same method as the synthesis method
  2. distillationThe solvent was distilled off under reduced pressure
  3. customthe resulting residue was purified by OH type silica gel chromatography (gradient elution with chloroform/methanol=100/0→94/6)
  4. customto obtain a crude product
  5. stirringthe mixture was stirred for 2.5 hours at room temperature
  6. stirringthe mixture was stirred overnight at room temperature
  7. extractionthe mixture was extracted with chloroform
  8. concentrationthe organic layer was concentrated under reduced pressure
  9. customThe resulting residue was purified by NH type silica gel chromatography (gradient elution with chloroform/methanol=100/0→94/6)

Sources & evidence

ORD record
ord-025720124c114304ac4343138e97ef4d
Source dataset
uspto-grants-2015_07
Patent number
US09073821B2

Reaction notes

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