(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acid → HCID 178495707, compound

HRID 1509727Notes

Reaction equation

HRID 1509727 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:7]([OH:9])=O)=[O:4].CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.[CH3:43][O:44][CH2:45][C@@H:46]1[CH2:50][N:49](C(OC(C)(C)C)=O)[C@H:48]([C:58]2[NH:59][C:60]([C:63]3[CH:68]=[C:67]4[CH2:69][O:70][C:71]5[CH:88]=[C:87]6[C:74]([CH:75]=[CH:76][C:77]7[N:81]=[C:80]([C@@H:82]8[CH2:86][CH2:85][CH2:84][NH:83]8)[NH:79][C:78]=76)=[CH:73][C:72]=5[C:66]4=[CH:65][CH:64]=3)=[CH:61][N:62]=2)[CH2:47]1>CCN(C(C)C)C(C)C.CN(C=O)C>[CH3:43][O:44][CH2:45][C@@H:46]1[CH2:50][NH:49][C@H:48]([C:58]2[NH:59][C:60]([C:63]3[CH:68]=[C:67]4[CH2:69][O:70][C:71]5[CH:88]=[C:87]6[C:74]([CH:75]=[CH:76][C:77]7[N:81]=[C:80]([C@@H:82]8[CH2:86][CH2:85][CH2:84][N:83]8[C:7](=[O:9])[C@H:6]([NH:5][C:3](=[O:4])[O:2][CH3:1])[C:10]8[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=8)[NH:79][C:78]=76)=[CH:73][C:72]=5[C:66]4=[CH:65][CH:64]=3)=[CH:61][N:62]=2)[CH2:47]1

Participants

6

Reactant 3

HCID 10910775(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acidHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 178495693HCID 178495693, compound

Product 1

HCID 178495707HCID 178495707, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Procedure

A mixture of (R)-2-(methoxycarbonylamino)-2-phenylacetic acid (22 mg, 0.105 mmol), COMU (45 mg, 0.069 mmol), and tert-butyl (2S,4S)-4-(methoxymethyl)-2-(5-{2-[(2S)-pyrrolidin-2-yl]-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl}-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (65 mg, 0.105 mmol) in 1.5 mL 10% DIPEA in DMF was stirred for 1.5h. The reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude intermediate was treated with 8 mL 1.25N HCl in ethanol at 50° C. for 4h. Added saturated sodium bicarbonate and extracted the free base into dichloromethane. (106 mg).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate
  2. dry with materialThe organic phase was dried over sodium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. additionThe crude intermediate was treated with 8 mL 1.25N HCl in ethanol at 50° C. for 4h
  6. extractionAdded saturated sodium bicarbonate and extracted the free base into dichloromethane

Sources & evidence

ORD record
ord-56b2a09ad6934891be629c6dcff07588
Source dataset
uspto-grants-2015_12
Patent number
US09221833B2

Reaction notes

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