Diisopropylethylamine → HCID 86670840, compound

HRID 709368Notes

Reaction equation

HRID 709368 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:22]([CH3:24])[CH3:23])[C:7]([N:9]1[CH:13]([C:14]([OH:16])=O)[CH2:12][C:11]2([CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[CH2:10]1)=[O:8])=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:50][CH2:51][C:52]([C:54]1[CH:59]=[CH:58][C:57]([Br:60])=[CH:56][CH:55]=1)=[O:53].CCN(C(C)C)C(C)C>[Cl-].[Na+].O.CN(C=O)C>[Br:60][C:57]1[CH:56]=[CH:55][C:54]([C:52](=[O:53])[CH2:51][NH:50][C:14]([CH:13]2[CH2:12][C:11]3([CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[CH2:10][N:9]2[C:7](=[O:8])[C@@H:6]([NH:5][C:3](=[O:4])[O:2][CH3:1])[CH:22]([CH3:24])[CH3:23])=[O:16])=[CH:59][CH:58]=1

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 27982162-Amino-1-(4-bromophenyl)ethan-1-one hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58313160HCID 58313160, compound

Product 1

HCID 86670840HCID 86670840, compoundYield 63.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

In a 50 mL flask, 2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-8-oxa-2-azaspiro[4.5]decane-3-carboxylic acid (200 mg, 584 μmol) was combined with DMF (5.00 ml) to give a colorless solution. HATU (222 mg, 584 μmol) was added and stirred at room temperature for 10 min followed by addition of 2-amino-1-(4-bromophenyl)ethanone HCl (146 mg, 584 μmol). DIPEA (264 mg, 357 μl, 2.04 mmol) was then added dropwise and the suspension became a yellow solution once the DIPEA was added. It was stirred at room temperature for 1 hr and poured into brine solution (80 ml) and extracted with EtOAc (2×60 ml). The organic layer was washed with brine and H2O, dried with MgSO4, filtered and concentrated in vacuo to give a yellow solid. It was purified on a silica gel column (CH2Cl2, 2%, 4%, 6% MeOH/CH2Cl2) to afford methyl (2S)-1-(3-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)-8-oxa-2-azaspiro[4.5]decan-2-yl)-3-methyl-1-oxobutan-2-ylcarbamate as a solid (200 mg, 63.6%). ESI-LRMS m/e calcd for C24H32BrN3O6 [M+] 538. found 539 [M+H+].

Workup

  1. customto give a colorless solution
  2. additionwas added
  3. stirringIt was stirred at room temperature for 1 hr
  4. extractionextracted with EtOAc (2×60 ml)
  5. washThe organic layer was washed with brine and H2O
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a yellow solid
  10. customIt was purified on a silica gel column (CH2Cl2, 2%, 4%, 6% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-12e9455b0b114577bccb9f65f41cf40e
Source dataset
uspto-grants-2015_11
Patent number
US09180193B2

Reaction notes

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