Glyoxylic acid, monohydrate → HCID 118093096, compound

HRID 708921Notes

Reaction equation

HRID 708921 reaction equation
C(OC([N:11]([CH2:13][C:14]1[CH:15]=[C:16]([NH:27][C:28]([O:30][CH2:31][C@@H:32]([C:34]2[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][C:35]=2[CH3:43])[CH3:33])=[O:29])[CH:17]=[C:18]([F:26])[C:19]=1[O:20][C@@H:21]([CH3:25])[CH2:22][O:23][CH3:24])[CH3:12])=O)C1C=CC=CC=1.[NH2:44][C:45]1[CH:46]=[C:47]2[C:52](=[CH:53][CH:54]=1)[C:51]([N:55]([C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])=[N:50][CH:49]=[CH:48]2.O.[C:71]([OH:75])(=[O:74])[CH:72]=O>CC#N.CN(C=O)C>[C:66]([O:65][C:63]([N:55]([C:56]([O:58][C:59]([CH3:60])([CH3:61])[CH3:62])=[O:57])[C:51]1[C:52]2[C:47](=[CH:46][C:45]([NH:44][CH:72]([C:37]3[CH:38]=[CH:39][C:34]([C@@H:32]([CH3:33])[CH2:31][O:30][C:28](=[O:29])[NH:27][C:16]4[CH:15]=[C:14]([CH2:13][NH:11][CH3:12])[C:19]([O:20][C@@H:21]([CH3:25])[CH2:22][O:23][CH3:24])=[C:18]([F:26])[CH:17]=4)=[C:35]([CH3:43])[CH:36]=3)[C:71]([OH:75])=[O:74])=[CH:54][CH:53]=2)[CH:48]=[CH:49][N:50]=1)=[O:64])([CH3:69])([CH3:68])[CH3:67]

Participants

6

Reactant 3

HCID 15620607Glyoxylic acid, monohydrateHCID 58717298tert-butyl N-(6-aminoisoquinolin-1-yl)-N-[(tert-butoxy)carbonyl]carbamateHCID 131733880HCID 131733880, compound

Product 1

HCID 118093096HCID 118093096, compoundYield 42.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

37D (309 mg, 0.518 mmol), Intermediate 1 (205 mg, 0.570 mmol), glyoxylic acid monohydrate (47.7 mg, 0.518 mmol) were dissolved in CH3CN (3 ml) and DMF (0.5 ml). The mixture was stirred at 85° C. 20 h, then concentrated and purified by prep HPLC. The desired fractions were combined, concentrated. The residue was dissolved in THF (8 mL). 10% Pd/C was added and the mixture was hydrogenated at 40 psi for 3 h. The mixture was filtered, concentrated and purified by prep HPLC to give 37E (185 mg, 0.222 mmol, 42.8% yield). MS (ESI) m/z: 834.4 (M+H)+.

Workup

  1. concentration20 h, then concentrated
  2. custompurified by prep HPLC
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in THF (8 mL)
  5. addition10% Pd/C was added
  6. filtrationThe mixture was filtered
  7. concentrationconcentrated
  8. custompurified by prep HPLC

Sources & evidence

ORD record
ord-f69b719e53cc424cab8e10e7ee935bb4
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

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