Hydrochloric Acid → HCID 86678351, compound

HRID 882592Notes

Reaction equation

HRID 882592 reaction equation
FC(F)(F)C(O)=O.[CH3:8][NH:9][C@H:10]([C:14]([NH:16][C@H:17]([C:21]([N:23]([C@@H:25]([C@@H:62]([CH3:65])[CH2:63][CH3:64])[C@H:26]([O:60][CH3:61])[CH2:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][C@H:31]1[C@H:35]([O:58][CH3:59])[C@@H:36]([CH3:57])[C:37]([NH:39][C@@:40]1([C:49]([N:51]2[CH2:56][CH2:55][CH2:54][CH2:53][O:52]2)=[O:50])[CH2:42][C@@H:41]1[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:38])=[O:29])[CH3:24])=[O:22])[CH:18]([CH3:20])[CH3:19])=[O:15])[CH:11]([CH3:13])[CH3:12].O=[CH:67][CH2:68][CH2:69][C:70]([OH:72])=[O:71].C([BH3-])#N.[Na+].Cl>O1CCOCC1.O.O>[C:70]([CH2:69][CH2:68][CH2:67][N:9]([CH3:8])[C@H:10]([C:14]([NH:16][C@H:17]([C:21]([N:23]([C@@H:25]([C@@H:62]([CH3:65])[CH2:63][CH3:64])[C@H:26]([O:60][CH3:61])[CH2:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][C@H:31]1[C@H:35]([O:58][CH3:59])[C@@H:36]([CH3:57])[C:37]([NH:39][C@@:40]1([C:49]([N:51]2[CH2:56][CH2:55][CH2:54][CH2:53][O:52]2)=[O:50])[CH2:42][C@@H:41]1[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)=[O:38])=[O:29])[CH3:24])=[O:22])[CH:18]([CH3:19])[CH3:20])=[O:15])[CH:11]([CH3:12])[CH3:13])([OH:72])=[O:71]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 11124-Oxobutanoic acid2×HCID 5003444Sodium cyanoborohydride2×HCID 86678352HCID 86678352, compound2×

Product 1

HCID 86678351HCID 86678351, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

50 mg (0.054 mmol) of N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(1S,2R)-1-(1,2-oxazinan-2-ylcarbonyl)-2-phenylcyclopropyl]amino}-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide trifluoroacetate (Intermediate 16) were dissolved in 8 ml of dioxane/water, and 70 ml (0.108 mmol) of a 15% solution of 4-oxobutanoic acid in water were added. The reaction mixture was subsequently stirred at 100° C. for 1 h. After cooling to RT, 3.7 mg (0.059 mmol) of sodium cyanoborohydride were added and the mixture was adjusted to a pH of 3 by adding about 300 μl of 0.1 N hydrochloric acid. The reaction mixture was then stirred at 100° C. for a further 2 h. After cooling, another 70 ml (0.108 mmol) of the 15% 4-oxobutanoic acid solution were added and the reaction mixture was again stirred at 100° C. for 1 h. Then a further 3.7 mg (0.059 mmol) of sodium cyanoborohydride were added and about 300 μl of 0.1 N hydrochloric acid were subsequently used to adjust the pH back to 3. The reaction mixture was then stirred at 100° C. for another 2 h. In the event of conversion still being incomplete, this procedure was repeated for a third time. The reaction mixture was finally concentrated and the residue was purified by means of preparative HPLC. In this way, 32 mg (65% of theory) of the title compound were obtained in the form of a colourless foam.

Workup

  1. temperatureAfter cooling to RT
  2. stirringThe reaction mixture was then stirred at 100° C. for a further 2 h
  3. temperatureAfter cooling
  4. stirringthe reaction mixture was again stirred at 100° C. for 1 h
  5. stirringThe reaction mixture was then stirred at 100° C. for another 2 h
  6. concentrationThe reaction mixture was finally concentrated
  7. customthe residue was purified by means of preparative HPLC

Sources & evidence

ORD record
ord-f4cd3fee534e4498b3f17381b9abb440
Source dataset
uspto-grants-2015_03
Patent number
US08992932B2

Reaction notes

Loading…