Methanol → Biphenyl-2-ylcarbamic Acid 1-(2-{[3-(4-{[(R)-2-(tert-Butyldimethyl-silanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-phenylcarbamoyl)propyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester

HRID 1055296Notes

Reaction equation

HRID 1055296 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH2:12][CH2:13][CH2:14][N:15]([CH3:42])[C:16]([CH2:18][CH2:19][N:20]2[CH2:25][CH2:24][CH:23]([O:26][C:27](=[O:41])[NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH2:22][CH2:21]2)=[O:17])=[O:11])=[CH:5][CH:4]=1)=O.C(O)(=O)C.[NH2:47][CH2:48][C@@H:49]([C:58]1[CH:67]=[CH:66][C:65]([OH:68])=[C:64]2[C:59]=1[CH:60]=[CH:61][C:62](=[O:69])[NH:63]2)[O:50][Si:51]([C:54]([CH3:57])([CH3:56])[CH3:55])([CH3:53])[CH3:52].CO.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.O>[C:54]([Si:51]([CH3:53])([CH3:52])[O:50][C@H:49]([C:58]1[CH:67]=[CH:66][C:65]([OH:68])=[C:64]2[C:59]=1[CH:60]=[CH:61][C:62](=[O:69])[NH:63]2)[CH2:48][NH:47][CH2:1][C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]([CH2:12][CH2:13][CH2:14][N:15]([CH3:42])[C:16]([CH2:18][CH2:19][N:20]2[CH2:21][CH2:22][CH:23]([O:26][C:27](=[O:41])[NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH2:24][CH2:25]2)=[O:17])=[O:11])=[CH:7][CH:8]=1)([CH3:57])([CH3:56])[CH3:55]

Participants

7

Reactant 4

HCID 887MethanolHCID 5049666Sodium triacetoxyborohydrideHCID 666722995-[(R)-2-amino-1-(tert-butyldimethylsilanyloxy)ethyl]-8-hydroxy-1H-quinolin-2-one acetateHCID 86646959Biphenyl-2-ylcarbamic Acid 1-(2-{[3-(4-Formylphenylcarbamoyl)-propyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester

Product 1

HCID 66770345Biphenyl-2-ylcarbamic Acid 1-(2-{[3-(4-{[(R)-2-(tert-Butyldimethyl-silanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-phenylcarbamoyl)propyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of biphenyl-2-ylcarbamic acid 1-(2-{[3-(4-formyl-phenylcarbamoyl)propyl]methylcarbamoyl}ethyl)piperidin-4-yl ester (91 mg, 0.16 mmol) in DCM (2 mL) was added 5-[(R)-2-amino-1-(tert-butyldimethylsilanyloxy)ethyl]-8-hydroxy-1H-quinolin-2-one acetic acid salt (101 mg, 0.256 mmol) (see, e.g., U.S. Patent Publication No. 2006/0035931 A1, published Feb. 16, 2006) followed by MeOH (1 mL). The resulting yellow solution was stirred at room temperature for 10 min and then sodium triacetoxyborohydride (89 mg, 0.40 mmol) was added and this mixture was stirred overnight. LC-MS (Method 2-90) showed product was present (Rt 3.25 min; m/z 889.8 [M+H]+). Water and DCM were added and the layers were separated. The organic layer was washed with water (2×) and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound, which was used without further purification.

Workup

  1. stirringthis mixture was stirred overnight
  2. customthe layers were separated
  3. washThe organic layer was washed with water (2×) and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9b348991c2044bf8a0161dfcfe9a8825
Source dataset
uspto-grants-2016_07
Patent number
US09394275B2

Reaction notes

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