Hydrochloric Acid → HCID 178495665, compound

HRID 1751729Notes

Reaction equation

HRID 1751729 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:10]([N:12]1[CH2:16][C@@H:15]([C:17]([F:20])([F:19])[F:18])[CH2:14][C@H:13]1[C:21]1[NH:22][C:23]([C:26]2[CH:31]=[C:30]3[CH2:32][O:33][C:34]4[CH:61]=[C:60]5[C:37]([CH:38]=[CH:39][C:40]6[N:44]=[C:43]([C@@H:45]7[CH2:49][C@H:48]([CH2:50][O:51][CH3:52])[CH2:47][N:46]7[C:53](OC(C)(C)C)=[O:54])[NH:42][C:41]=65)=[CH:36][C:35]=4[C:29]3=[CH:28][CH:27]=2)=[CH:24][N:25]=1)=[O:11])[CH:7]([CH3:9])[CH3:8])=[O:4].Cl.[CH3:63][O:64][C:65]([NH:67][C@H:68]([C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=1)C(O)=O)=[O:66].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(=O)(O)[O-].[Na+]>O1CCOCC1.CN(C=O)C.C(OCC)C>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:7]([CH3:9])[CH3:8])[C:10]([N:12]1[CH2:16][C@@H:15]([C:17]([F:20])([F:19])[F:18])[CH2:14][C@H:13]1[C:21]1[NH:22][C:23]([C:26]2[CH:31]=[C:30]3[CH2:32][O:33][C:34]4[CH:61]=[C:60]5[C:37]([CH:38]=[CH:39][C:40]6[N:44]=[C:43]([C@@H:45]7[CH2:49][C@H:48]([CH2:50][O:51][CH3:52])[CH2:47][N:46]7[C:53](=[O:54])[C@H:68]([NH:67][C:65](=[O:66])[O:64][CH3:63])[C:72]7[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=7)[NH:42][C:41]=65)=[CH:36][C:35]=4[C:29]3=[CH:28][CH:27]=2)=[CH:24][N:25]=1)=[O:11])=[O:4]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 10910775(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acidHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 178495666tert-butyl (2S,4S)-2-(9-{2-[(2S,4S)-1-[N-(methoxycarbonyl)-L-valyl]-4-(trifluoromethyl)pyrrolidin-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

Product 1

HCID 178495665HCID 178495665, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-butyl (2S,4S)-2-(9-{2-[(2S,4S)-1-[N-(methoxycarbonyl)-L-valyl]-4-(trifluoromethyl)pyrrolidin-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 (<0.412 mmol, crude from previous step) was treated with 6 mL 4N HCl in dioxane at room temperature overnight and then at 50° C. for 1 hour. Diethyl ether (20 mL) was added and the precipitate of hydrochloride salt was collected by vacuum filtration. (126 mg, 0.16 mmol). This material was combined with (R)-2-(methoxycarbonylamino)-2-phenylacetic acid (34 mg, 0.16 mmol), COMU (70 mg, 0.16 mmol), and 1.6 mL of 10% DIPEA in DMF. After 1 hour at room temperature, the mixture was added dropwise into 25 mL saturated sodium bicarbonate, with stirring and the resulting precipitate was collected by vacuum filtration and washed with 2 mL water. The product was purified, then re-purified by reverse phase HPLC. (3.5 mg).

Workup

  1. filtrationthe precipitate of hydrochloride salt was collected by vacuum filtration
  2. waitAfter 1 hour at room temperature
  3. filtrationthe resulting precipitate was collected by vacuum filtration
  4. washwashed with 2 mL water
  5. customThe product was purified
  6. customre-purified by reverse phase HPLC

Sources & evidence

ORD record
ord-ad7c00cf05ee470fadd885050919cbb5
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

Loading…