Diisopropylethylamine → HCID 117607971, compound

HRID 58792Notes

Reaction equation

HRID 58792 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:54][C:55](=[O:63])[CH2:56][N:57]1[CH2:62][CH2:61][O:60][CH2:59][CH2:58]1)[C:37]([NH:39][C@@H:40]([CH2:44][C:45]1[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[C:47]([OH:53])[CH:46]=1)[C:41](O)=[O:42])=[O:38].[NH2:64][C@@H:65]([CH2:72][C:73]1[CH2:78][CH2:77][CH2:76][CH2:75][CH:74]=1)[C:66]([C@@:68]1([CH3:71])[CH2:70][O:69]1)=[O:67]>CN(C=O)C.O.CCOC(C)=O>[C:73]1([CH2:72][C@H:65]([NH:64][C:41](=[O:42])[C@@H:40]([NH:39][C:37](=[O:38])[C@@H:36]([NH:54][C:55](=[O:63])[CH2:56][N:57]2[CH2:58][CH2:59][O:60][CH2:61][CH2:62]2)[CH2:35][OH:34])[CH2:44][C:45]2[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[C:47]([OH:53])[CH:46]=2)[C:66]([C@@:68]2([CH3:71])[CH2:70][O:69]2)=[O:67])[CH2:78][CH2:77][CH2:76][CH2:75][CH:74]=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 117607990HCID 117607990, compoundHCID 117607998HCID 117607998, compound

Product 1

HCID 117607971HCID 117607971, compoundYield 35.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (570 mg, 1.5 mmol) and DIPEA (1.48 mL) were added to a solution of (S)-2-((S)-3-hydroxy-2-(2-morpholinoacetamido)propanamido)-3-(3-hydroxy-4-methoxyphenyl)propanoic acid (425 mg, 1 mmol) and (S)-2-amino-3-(cyclohex-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)propan-1-one (TFA salt, 1 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) and 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-(3-hydroxy-4-methoxyphenyl)propanamide (220 mg, 35% yield). 1H NMR (300 MHz, DMSO-d6): δ 8.74 (s, 1H), 8.22 (d, J=7.5 Hz, 1H), 8.02 (d, J=8.1 Hz, 1H), 7.78 (m, 1H), 6.73 (d, J=8.4 Hz, 1H), 6.63 (s, 1H), 6.54 (m, 1H), 5.39 (m, 1H), 5.03 (m, 1H), 4.40-4.60 (m, 2H), 4.30 (m, 1H), 3.71 (s, 3H), 3.60 (m, 4H), 3.50 (m, 2H), 3.22 (m, 1H), 2.80-3.10 (m, 3H), 2.40 (m, 3H), 2.20 (m, 2H), 1.90-2.10 (m, 4H), 1.50-1.70 (m, 4H), 1.37 (s, 3H), 1.00-1.30 (m, 3H). MS (EI) for C31H44N4O9, found 617.3 (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-2a61968578194d04862dcbd0ac774f98
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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