Diisopropylethylamine → HCID 117607982, compound

HRID 58793Notes

Reaction equation

HRID 58793 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[OH:34][CH2:35][C@H:36]([NH:40][C:41](=[O:49])[CH2:42][N:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1)[C:37]([OH:39])=O.[NH2:50][C@@H:51]([CH2:69][C:70]1[CH:75]=[CH:74][C:73]([S:76]([CH3:79])(=[O:78])=[O:77])=[CH:72][CH:71]=1)[C:52]([NH:54][C@@H:55]([CH2:62][C:63]1[CH2:68][CH2:67][CH2:66][CH2:65][CH:64]=1)[C:56]([C@@:58]1([CH3:61])[CH2:60][O:59]1)=[O:57])=[O:53]>CN(C=O)C.O.CCOC(C)=O>[C:63]1([CH2:62][C@H:55]([NH:54][C:52](=[O:53])[C@@H:51]([NH:50][C:37](=[O:39])[C@@H:36]([NH:40][C:41](=[O:49])[CH2:42][N:43]2[CH2:48][CH2:47][O:46][CH2:45][CH2:44]2)[CH2:35][OH:34])[CH2:69][C:70]2[CH:75]=[CH:74][C:73]([S:76]([CH3:79])(=[O:77])=[O:78])=[CH:72][CH:71]=2)[C:56]([C@@:58]2([CH3:61])[CH2:60][O:59]2)=[O:57])[CH2:68][CH2:67][CH2:66][CH2:65][CH:64]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117608224HCID 117608224, compoundHCID 117608234HCID 117608234, compound

Product 1

HCID 117607982HCID 117607982, compoundYield 35%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (502 mg, 1.3 mmol) and DIPEA (1.35 mL) were added to a solution of (S)-3-hydroxy-2-(2-morpholinoacetamido)propanoic acid (225 mg, 0.97 mmol) and (S)-2-amino-N-((S)-3-(cyclohex-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-(4-(methylsulfonyl)phenyl)propanamide (0.88 mmol) in DMF (20 mL) at 0° C. with stirring. The reaction mixture was allowed to warm to ambient temperature and stirred for 3 h. EtOAc (100 mL) and water (100 mL) was added and the two layers were separated. The aqueous phase was extracted with EtOAc (50 mL×3). The combined organic phases were washed with brine (200 mL×3), dried over anhydrous sodium sulfate and concentrated. The residue was purified by flash column chromatography on silica gel (CH2Cl2/EtOAc/MeOH=20:10:0.2) to afford (S)-N-((S)-3-(cyclohex-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-2-((S)-3-hydroxy-2-(2-morpholinoacetamido)propanamido)-3-(4-(methylsulfonyl)phenyl)propanamide (200 mg, 35% yield). 1H NMR (300 MHz, DMSO-d6): δ 8.33 (d, J=7.2 Hz, 1H), 8.13 (d, J=8.4 Hz, 1H), 7.78 (d, J=8.1 Hz, 2H), 7.69 (d, J=7.8 Hz, 1H), 7.46 (d, J=7.8 Hz, 2H), 5.40 (m, 1H), 5.05 (m, 1H), 4.45-4.70 (m, 2H), 4.30 (m, 1H), 3.57 (m, 4H), 3.50 (m, 2H), 3.22 (m, 1H), 3.20 (s, 3H), 3.10 (m, 1H), 2.80-3.00 (m, 4H), 2.40 (m, 2H), 2.20 (m, 2H), 1.90-2.10 (m, 4H), 1.50-1.70 (m, 3H), 1.37 (s, 3H), 1.00-1.30 (m, 3H). MS (EI) for C31H44N4O9S, found 649.0 (MH)+.

Workup

  1. stirringstirred for 3 h
  2. customthe two layers were separated
  3. extractionThe aqueous phase was extracted with EtOAc (50 mL×3)
  4. washThe combined organic phases were washed with brine (200 mL×3)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography on silica gel (CH2Cl2/EtOAc/MeOH=20:10:0.2)

Sources & evidence

ORD record
ord-8fda109760ef4c87b2b5408d8ddd5bd5
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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