Hydrochloric Acid → HCID 66547737, compound

HRID 573016Notes

Reaction equation

HRID 573016 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@H:40](/[CH:48]=[CH:49]\[CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=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>[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@H:40](/[CH:48]=[CH:49]\[CH2:50][C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)[CH2:41][C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)=[O:38])=[O:29])[CH3:24])=[O:22])[CH:18]([CH3:19])[CH3:20])=[O:15])[CH:11]([CH3:13])[CH3:12])([OH:72])=[O:71]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 11124-Oxobutanoic acidHCID 5003444Sodium cyanoborohydride2×HCID 86712507HCID 86712507, compound2×

Product 1

HCID 66547737HCID 66547737, compound

Reagents, catalysts & solvents 1

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

Conditions

Temperature
100 °C

Procedure

14.5 mg (16 μmol) N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S,3Z)-1,5-diphenylpent-3-en-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide trifluoroacetic acid salt (intermediate 17) was dissolved in 1 mL dioxane/water (1:1) and mixed with 20.4 μL (32 μmol) of a 15% aqueous solution of 4-oxobutanoic acid. The batch was then stirred for one hour at 100° C. After cooling to RT, 1.1 mg (17 μmol) sodium cyanoborohydride was added and the mixture was adjusted to a pH of 3 by adding approx. 150 μL 0.1N hydrochloric acid. The batch was then stirred for two hours more at 100° C. Then 1.1 mg (17 μmol) sodium cyanoborohydride was added again and the mixture was next adjusted to a pH of 3 by adding approx. 300 μL 0.1N hydrochloric acid. The batch was then stirred again for two hours at 100° C. If the reaction was still incomplete, this procedure was repeated once more. Finally, the batch was concentrated and the raw product was purified by preparative HPLC and lyophilized from dioxane, thereby yielding 13.1 mg (93% of the theoretical) of the title compound in the form of a white solid.

Workup

  1. temperatureAfter cooling to RT
  2. stirringThe batch was then stirred for two hours more at 100° C
  3. stirringThe batch was then stirred again for two hours at 100° C
  4. concentrationFinally, the batch was concentrated
  5. customthe raw product was purified by preparative HPLC

Sources & evidence

ORD record
ord-05976446c9f9417893f19f35681f4bc2
Source dataset
uspto-grants-2015_05
Patent number
US09029406B2

Reaction notes

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