Diisopropylethylamine → HCID 178455974, compound

HRID 1413023Notes

Reaction equation

HRID 1413023 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:11]([N:13]1[CH2:17][C@@H:16]([CH3:18])[CH2:15][C@H:14]1[C:19]1[NH:20][C:21]([C:24]2[CH:29]=[C:28]3[CH2:30][O:31][C:32]4[CH:59]=[C:58]5[C:35]([CH:36]=[CH:37][C:38]6[N:42]=[C:41]([C@@H:43]7[CH2:47][C@H:46]([CH2:48][O:49][CH3:50])[CH2:45][N:44]7[C:51](OC(C)(C)C)=[O:52])[NH:40][C:39]=65)=[CH:34][C:33]=4[C:27]3=[CH:26][CH:25]=2)=[CH:22][N:23]=1)=[O:12])[C@@H:7]([CH2:9][CH3:10])[CH3:8])=[O:4].[CH3:60][O:61][C:62]([NH:64][C@H:65]([C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)C(O)=O)=[O:63].CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>Cl.CCO>[CH3:60][O:61][C:62](=[O:63])[NH:64][C@H:65]([C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)[C:51]([N:44]1[CH2:45][C@@H:46]([CH2:48][O:49][CH3:50])[CH2:47][C@H:43]1[C:41]1[NH:40][C:39]2[C:58]3[C:35]([CH:36]=[CH:37][C:38]=2[N:42]=1)=[CH:34][C:33]1[C:27]2[C:28]([CH2:30][O:31][C:32]=1[CH:59]=3)=[CH:29][C:24]([C:21]1[NH:20][C:19]([C@@H:14]3[CH2:15][C@H:16]([CH3:18])[CH2:17][N:13]3[C:11](=[O:12])[C@@H:6]([NH:5][C:3]([O:2][CH3:1])=[O:4])[C@H:7]([CH3:8])[CH2:9][CH3:10])=[N:23][CH:22]=1)=[CH:25][CH:26]=2)=[O:52]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 10910775(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acidHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 178455977HCID 178455977, compound

Product 1

HCID 178455974HCID 178455974, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent

Procedure

A solution of tert-butyl(2S,4S)-2-[9-(2-{(2S,4S)-1-[N-(methoxycarbonyl)-L-alloisoleucyl]-4-methylpyrrolidin-2-yl}-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]-4-(methoxymethyl)pyrrolidine-1-carboxylate (218 mg, 0.27 mmol) in 1.25 N HCl in EtOH (3 mL) was heated to 50° C. for 3 h. The reaction was concentrated and the crude material dissolved in DMF (3 mL). To this solution was added a solution of (R)-2-(methoxycarbonylamino)-2-phenylacetic acid (73 mg, 0.35 mmol) and COMU (127 mg, 0.30 mmol). To the resulting solution was added diisopropylethylamine (0.141 mL, 0.81 mmol). After stirring for 2 h at room temperature, the reaction was quenched with 1N HCl (0.200 mL) and purified by HPLC. After lyophilization, the TFA salt was dissolved in EtOAc and washed with saturated NaHCO3. The organic phase was dried over Na2SO4 and concentrated. The free base was then dissolved in MeCN/H2O and lyophilized to afford methyl{(1R)-2-[(2S,4S)-2-(9-{2-[(2S,4S)-1-{(2S,3R)-2-[(methoxycarbonyl)amino]-3-methylpentanoyl}-4-methylpyrrolidin-2-yl]-1H-imidazol-5-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl]-2-oxo-1-phenylethyl}carbamate

Workup

  1. concentrationThe reaction was concentrated
  2. dissolutionthe crude material dissolved in DMF (3 mL)
  3. customthe reaction was quenched with 1N HCl (0.200 mL)
  4. custompurified by HPLC
  5. dissolutionAfter lyophilization, the TFA salt was dissolved in EtOAc
  6. washwashed with saturated NaHCO3
  7. dry with materialThe organic phase was dried over Na2SO4
  8. concentrationconcentrated
  9. dissolutionThe free base was then dissolved in MeCN/H2O

Sources & evidence

ORD record
ord-481b19dc58c947599e9805faaceb5c7e
Source dataset
uspto-grants-2014_12
Patent number
US08921341B2

Reaction notes

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