Triethylamine → (R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid((1S,2R)-1-{1-[5-(1,3-dimethyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-cyclopropylcarbamoyl}-2-hydroxy-propyl)-amide

HRID 2038812Notes

Reaction equation

HRID 2038812 reaction equation
[C:1]([C:3]1[CH:31]=[CH:30][C:6]([CH2:7][C@@:8]2([CH3:29])[N:12]3[C:13]([C:16]([OH:18])=O)=[CH:14][N:15]=[C:11]3[N:10]([C:19]3[CH:24]=[C:23]([Cl:25])[C:22]([F:26])=[C:21]([Cl:27])[CH:20]=3)[C:9]2=[O:28])=[CH:5][CH:4]=1)#[N:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(CC)CC.Cl.[NH2:62][C@@H:63]([C@H:83]([OH:85])[CH3:84])[C:64]([NH:66][C:67]1([C:70]2[N:75]=[CH:74][C:73]([C:76]3[C:77]([CH3:82])=[N:78][N:79]([CH3:81])[CH:80]=3)=[CH:72][N:71]=2)[CH2:69][CH2:68]1)=[O:65]>C1COCC1>[CH3:81][N:79]1[CH:80]=[C:76]([C:73]2[CH:74]=[N:75][C:70]([C:67]3([NH:66][C:64]([C@@H:63]([NH:62][C:16]([C:13]4[N:12]5[C@@:8]([CH2:7][C:6]6[CH:30]=[CH:31][C:3]([C:1]#[N:2])=[CH:4][CH:5]=6)([CH3:29])[C:9](=[O:28])[N:10]([C:19]6[CH:24]=[C:23]([Cl:25])[C:22]([F:26])=[C:21]([Cl:27])[CH:20]=6)[C:11]5=[N:15][CH:14]=4)=[O:18])[C@H:83]([OH:85])[CH3:84])=[O:65])[CH2:68][CH2:69]3)=[N:71][CH:72]=2)[C:77]([CH3:82])=[N:78]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 58431190(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acidHCID 67515442(2s,3r)-2-Amino-n-{1-[5-(1,3-dimethyl-1h-pyrazol-4-yl)-pyrimidin-2-yl]-cyclopropyl}-3-hydroxy-butyramide hydrochloride

Product 1

HCID 49832099(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid((1S,2R)-1-{1-[5-(1,3-dimethyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-cyclopropylcarbamoyl}-2-hydroxy-propyl)-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a flask was added (R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid (0.80 g, 2.18 mmol), TBTU (0.73 g, 2.28 mmol) and Et3N (0.91 mL, 6.54 mmol) and THF (10 mL). The mixture was allowed to stir at RT for 30 min. The mixture was transferred to a separate flask containing (2S,3R)-2-amino-N-{1-[5-(1,3-dimethyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-cyclopropyl}-3-hydroxy-butyramide hydrochloride (1.0 g, 2.18 mmol) in THF (30 mL). The mixture was stirred at RT for 24 h. The mixture was concentrated and purified by silica gel chromatography to provide 1.45 g of the title compound as a white solid following removal of the solvent, m/z=771.8 [M+H]+.

Workup

  1. customThe mixture was transferred to a separate flask
  2. stirringThe mixture was stirred at RT for 24 h
  3. concentrationThe mixture was concentrated
  4. custompurified by silica gel chromatography
  5. customto provide
  6. custom1.45 g of the title compound as a white solid following removal of the solvent, m/z=771.8 [M+H]+

Sources & evidence

ORD record
ord-cf26f0ea4795441fb57ffe45b1304662
Source dataset
uspto-grants-2013_11
Patent number
US08575360B2

Reaction notes

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