Hydrochloric Acid → HCID 67682575, compound

HRID 1751596Notes

Reaction equation

HRID 1751596 reaction equation
C([C@:5]1([C:23]2[NH:24][C:25]([C:28]3[CH:33]=[CH:32][C:31]([C:34]4[CH:39]=[CH:38][C:37]([C:40]5[NH:44][C:43]([C@@H:45]6[CH2:49][CH2:48][CH2:47][N:46]6[C:50](=[O:60])[C@@H:51]([NH:55][C:56](=[O:59])[O:57][CH3:58])[CH:52]([CH3:54])[CH3:53])=[N:42][CH:41]=5)=[CH:36][CH:35]=4)=[CH:30][CH:29]=3)=[CH:26][N:27]=2)[CH2:9][C@H:8]([CH2:10][O:11][CH3:12])[CH2:7][N:6]1[C:13](=[O:22])[C@H:14]([NH2:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(C)(C)C.Cl.[CH:62]1([C:65]([OH:67])=O)[CH2:64][CH2:63]1.CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.CO>[CH:62]1([C:65]([NH:21][C@H:14]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:13]([N:6]2[CH2:7][C@@H:8]([CH2:10][O:11][CH3:12])[CH2:9][C@H:5]2[C:23]2[NH:24][C:25]([C:28]3[CH:29]=[CH:30][C:31]([C:34]4[CH:35]=[CH:36][C:37]([C:40]5[NH:44][C:43]([C@@H:45]6[CH2:49][CH2:48][CH2:47][N:46]6[C:50](=[O:60])[C@@H:51]([NH:55][C:56](=[O:59])[O:57][CH3:58])[CH:52]([CH3:54])[CH3:53])=[N:42][CH:41]=5)=[CH:38][CH:39]=4)=[CH:32][CH:33]=3)=[CH:26][N:27]=2)=[O:22])=[O:67])[CH2:64][CH2:63]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 15655Cyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 86708786HCID 86708786, compound

Product 1

HCID 67682575HCID 67682575, compoundYield 36.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To methyl (S)-1-((S)-2-(5-(4′-(2-((2S,4S)-(tert-butyl)-1-((R)-2-amino-2-phenylacetyl)-4-(methoxymethyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (187 mg, 0.22 mmol) in DCM (5 mL) and MeOH (1 mL) was added HCl (4M in dioxane, 1.0 mL). The solution was stirred for 16 h, and the solvent was removed. The intermediate was dissolved in DMF (5 mL). Cyclopropanecarboxylic acid (34 μL, 0.44 mmol), COMU (104 mg, 0.22 mmol), and DIPEA (0.19 mL, 1.09 mmol) were added sequentially. The solution stirred for 30 min. It was purified by HPLC to yield product (66.5 mg). LCMS-ESI+: calc'd for C47H50N8O7: 826.98 (M+); Found: 827.37 (M+H+).

Workup

  1. customthe solvent was removed
  2. dissolutionThe intermediate was dissolved in DMF (5 mL)
  3. stirringThe solution stirred for 30 min
  4. customIt was purified by HPLC

Sources & evidence

ORD record
ord-bb6a9199af31480b98643d27181b9f49
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

Loading…