Trifluoroacetic acid → HCID 59481319, compound

HRID 1476046Notes

Reaction equation

HRID 1476046 reaction equation
C(O)(C(F)(F)F)=O.[CH3:8][CH:9]([CH3:52])[C@H:10]([NH:45][C:46]1[N:51]=[CH:50][CH:49]=[CH:48][N:47]=1)[C:11]([N:13]1[CH2:17][CH2:16][CH2:15][C@H:14]1[C:18]1[NH:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][C:32]([C:35]4[NH:39][C:38]([C@@H:40]5[CH2:44][CH2:43][CH2:42][NH:41]5)=[N:37][CH:36]=4)=[CH:31][CH:30]=3)=[CH:25][CH:24]=2)=[CH:21][N:22]=1)=[O:12].CCN(C(C)C)C(C)C.[CH3:62][O:63][C:64]([NH:66][C@@H:67]([CH:71]([CH3:73])[CH3:72])[C:68](O)=[O:69])=[O:65].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CO.CC#N.O>[CH3:62][O:63][C:64](=[O:65])[NH:66][C@H:67]([C:68]([N:41]1[CH2:42][CH2:43][CH2:44][C@H:40]1[C:38]1[NH:39][C:35]([C:32]2[CH:31]=[CH:30][C:29]([C:26]3[CH:27]=[CH:28][C:23]([C:20]4[NH:19][C:18]([C@@H:14]5[CH2:15][CH2:16][CH2:17][N:13]5[C:11](=[O:12])[C@H:10]([CH:9]([CH3:52])[CH3:8])[NH:45][C:46]5[N:51]=[CH:50][CH:49]=[CH:48][N:47]=5)=[N:22][CH:21]=4)=[CH:24][CH:25]=3)=[CH:34][CH:33]=2)=[CH:36][N:37]=1)=[O:69])[CH:71]([CH3:73])[CH3:72]

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 24898195HCID 24898195, compound

Product 1

HCID 59481319HCID 59481319, compoundYield 32.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To a solution of the TFA salt of (S)-3-methyl-2-(pyrimidin-2-ylamino)-1-((S)-2-(5-(4′-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-1-one (cj-10) (0.208 g, 0.197 mmol) in DMF (4 mL) was added iPr2NEt (0.20 mL, 1.15 mmol), (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (0.049 g, 0.28 mmol) and HATU (0.105 g, 0.276 mmol). The solution was stirred for 1.5 h at room temperature, diluted with MeOH (2 mL) and purified directly by prep HPLC (Luna 5 u C18/MeCN—H2O—NH4OAc). This material was repurified by flash chromatography (SiO2/2-10% MeOH—CH2Cl2) to give a solid which was lyophilized from CH3CN—H2O to give the title compound (48.6 mg, 32%) as a colourless solid.

Workup

  1. custompurified directly by prep HPLC (Luna 5 u C18/MeCN—H2O—NH4OAc)
  2. customThis material was repurified by flash chromatography (SiO2/2-10% MeOH—CH2Cl2)
  3. customto give a solid which

Sources & evidence

ORD record
ord-b59dda40178d43cc8fedd8c6323b849f
Source dataset
uspto-grants-2015_04
Patent number
US09018390B2

Reaction notes

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