Diisopropylethylamine → HCID 86679252, compound

HRID 1519663Notes

Reaction equation

HRID 1519663 reaction equation
CCN(C(C)C)C(C)C.[C:10]([C@:13]([N:19]([CH3:29])[C:20]([C:22]1[CH:27]=[CH:26][C:25]([I:28])=[CH:24][CH:23]=1)=[O:21])([CH3:18])[C:14]([NH:16][CH3:17])=[O:15])([OH:12])=O.[O:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]1[O:36][NH2:37].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(OCC)(=O)C.O.CN(C=O)C>[I:28][C:25]1[CH:26]=[CH:27][C:22]([C:20]([N:19]([CH3:29])[C@:13]([CH3:18])([C:10]([NH:37][O:36][CH:31]2[CH2:32][CH2:33][CH2:34][CH2:35][O:30]2)=[O:12])[C:14]([NH:16][CH3:17])=[O:15])=[O:21])=[CH:23][CH:24]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712681871-{[(2S)-2-carboxy-1-(methylamino)-1-oxopropan-2-yl](methyl)carbamoyl}-4-iodobenzene2×

Product 1

HCID 86679252HCID 86679252, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIPEA (5.3 mL) was added to a DMF (16 mL) solution of 1-{[(2S)-2-carboxy-1-(methylamino)-1-oxopropan-2-yl](methyl)carbamoyl}-4-iodobenzene (Intermediate 14, 4.0 g) and O-(tetrahydropyran-2-yl)hydroxylamine (1.6 g), and HATU (5.9 g) was added under water cooling. The mixture was stirred for 2 hours under ice cooling, and then stirred for 1 hour at room temperature. Water and ethyl acetate were sequentially added, and the organic layer was isolated. The extract was washed sequentially with water and brine, and dried over anhydrous sodium sulfate. OH type silica gel (4.0 g) was added, and the mixture was filtered for 10 minutes at room temperature. Then, the silica gel was filtered out, and the solvent was distilled off under reduced pressure. A mixed solvent (IPE:ethyl acetate=10:1) was added to the resulting residue, and the supernatant was removed. This procedure was repeated twice, and then a solvent mixture of ethyl acetate (6.0 mL) and IPA (6.0 mL) was added to the resulting residue. The solids were collected by filtration to obtain (2S)-2-[(4-iodobenzoyl)(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (Intermediate 15, white solid) (1.3 g, 26%). Moreover, the residue obtained from the filtrate was purified by OH type silica gel column chromatography (ethyl acetate/hexane=50/50→gradient elution with chloroform/acetone=100/0→85/15) to obtain (2S)-2-[(4-iodobenzoyl)(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (Intermediate 15, white solid) (1.7 g, 34%).

Workup

  1. additionwas added under water cooling
  2. stirringstirred for 1 hour at room temperature
  3. customthe organic layer was isolated
  4. washThe extract was washed sequentially with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. additionOH type silica gel (4.0 g) was added
  7. filtrationthe mixture was filtered for 10 minutes at room temperature
  8. filtrationThen, the silica gel was filtered out
  9. distillationthe solvent was distilled off under reduced pressure
  10. additionA mixed solvent (IPE:ethyl acetate=10:1) was added to the resulting residue
  11. customthe supernatant was removed
  12. additiona solvent mixture of ethyl acetate (6.0 mL) and IPA (6.0 mL)
  13. additionwas added to the resulting residue
  14. filtrationThe solids were collected by filtration

Sources & evidence

ORD record
ord-ea8b98e0cd904f7c96e57b6b3e230d48
Source dataset
uspto-grants-2015_07
Patent number
US09073821B2

Reaction notes

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