Hydrochloric Acid → HCID 86708786, compound

HRID 1751595Notes

Reaction equation

HRID 1751595 reaction equation
C(OC([N:8]1[CH2:12][C@@H:11]([CH2:13][O:14][CH3:15])[CH2:10][C@H:9]1[C:16]1[NH:17][C:18]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][C:30]([C:33]4[NH:37][C:36]([C@@H:38]5[CH2:42][CH2:41][CH2:40][N:39]5[C:43](=[O:53])[C@@H:44]([NH:48][C:49]([O:51][CH3:52])=[O:50])[CH:45]([CH3:47])[CH3:46])=[N:35][CH:34]=4)=[CH:29][CH:28]=3)=[CH:23][CH:22]=2)=[CH:19][N:20]=1)=O)(C)(C)C.Cl.C(OC([NH:62][C@H:63]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)[C:64]([OH:66])=O)=O)(C)(C)C.CCO[C:76]([C:78]([C:91]#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.[CH3:100]CN(C(C)C)C(C)C>C(Cl)Cl.CO.CO.CCOC(C)=O>[CH3:52][O:51][C:49](=[O:50])[NH:48][C@@H:44]([CH:45]([CH3:47])[CH3:46])[C:43]([N:39]1[CH2:40][CH2:41][CH2:42][C@H:38]1[C:36]1[NH:37][C:33]([C:30]2[CH:31]=[CH:32][C:27]([C:24]3[CH:25]=[CH:26][C:21]([C:18]4[NH:17][C:16]([C@@:9]5([C:78]([CH3:91])([CH3:100])[CH3:76])[CH2:10][C@H:11]([CH2:13][O:14][CH3:15])[CH2:12][N:8]5[C:64](=[O:66])[C@H:63]([NH2:62])[C:67]5[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=5)=[N:20][CH:19]=4)=[CH:22][CH:23]=3)=[CH:28][CH:29]=2)=[CH:34][N:35]=1)=[O:53]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2755953(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acidHCID 69675589HCID 69675589, compoundHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate

Product 1

HCID 86708786HCID 86708786, compoundYield 88.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

To (2S,4S)-tert-butyl-2-(5-(4′-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (191 mg, 0.26 mmol) in DCM (5 mL) and MeOH (1 mL) was added HCl (4M in dioxane, 1.0 mL). The solution stirred for 16 h, and the solvent was removed. The intermediate was dissolved in DMF (5 mL). (R)-2-(tert-butoxycarbonylamino)-2-phenylacetic acid (65 mg, 0.26 mmol), COMU (124 mg, 0.26 mmol), and DIPEA (0.23 mL, 1.3 mmol) were added sequentially. The solution stirred for 2 h., diluted with MeOH/EtOAc (1:10), washed with sat. NaHCO3 twice, brine, dried over MgSO4 and concentrated. It was purified by silica gel chromatography to yield product (187 mg).

Workup

  1. customthe solvent was removed
  2. dissolutionThe intermediate was dissolved in DMF (5 mL)
  3. stirringThe solution stirred for 2 h.
  4. washwashed with sat. NaHCO3 twice
  5. dry with materialbrine, dried over MgSO4
  6. concentrationconcentrated
  7. customIt was purified by silica gel chromatography

Sources & evidence

ORD record
ord-6faf4ffa67e64d66b1cd6740adba71ff
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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