Sodium Bicarbonate → HCID 86678371, compound

HRID 882617Notes

Reaction equation

HRID 882617 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]([CH3:65])[C@H:9]([C:13]([NH:15][C@H:16]([C:20]([N:22]([C@@H:24]([C@@H:61]([CH3:64])[CH2:62][CH3:63])[C@H:25]([O:59][CH3:60])[CH2:26][C:27]([N:29]1[CH2:33][CH2:32][CH2:31][C@H:30]1[C@H:34]([O:57][CH3:58])[C@@H:35]([CH3:56])[C:36]([NH:38][C@@:39]1([C:48]([N:50]2[CH2:55][CH2:54][CH2:53][CH2:52][O:51]2)=[O:49])[CH2:41][C@@H:40]1[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:37])=[O:28])[CH3:23])=[O:21])[CH:17]([CH3:19])[CH3:18])=[O:14])[CH:10]([CH3:12])[CH3:11].C(=O)([O-])O.[Na+].[O:71]=[C:72]1[CH:76]=[CH:75][C:74](=[O:77])N1C(OC)=O>O1CCOCC1.O>[O:71]=[C:72]1[CH:76]=[CH:75][C:74](=[O:77])[N:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]([CH3:65])[C@H:9]([C:13]([NH:15][C@H:16]([C:20]([N:22]([C@@H:24]([C@@H:61]([CH3:64])[CH2:62][CH3:63])[C@H:25]([O:59][CH3:60])[CH2:26][C:27]([N:29]1[CH2:33][CH2:32][CH2:31][C@H:30]1[C@H:34]([O:57][CH3:58])[C@@H:35]([CH3:56])[C:36]([NH:38][C@@:39]1([C:48]([N:50]2[CH2:55][CH2:54][CH2:53][CH2:52][O:51]2)=[O:49])[CH2:41][C@@H:40]1[C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)=[O:37])=[O:28])[CH3:23])=[O:21])[CH:17]([CH3:18])[CH3:19])=[O:14])[CH:10]([CH3:12])[CH3:11]

Participants

5

Reactant 3

HCID 516892Sodium Bicarbonate2×HCID 580610N-(Methoxycarbonyl)maleimide2×HCID 86678372HCID 86678372, compound2×

Product 1

HCID 86678371HCID 86678371, compound

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent2×

Procedure

64 mg (70 μmol) of N-(6-aminohexyl)-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 (Intermediate 97) were taken up in 3 ml of 1:1 dioxane/water, then adjusted to pH 9 with 4 ml of saturated sodium hydrogencarbonate solution and subsequently admixed with 16.3 mg (110 μmol) of methyl 2,5-dioxo-2,5-dihydro-1H-pyrrole-1-carboxylate. The reaction mixture was stirred at RT for 1 h and then concentrated under reduced pressure. Then another 8 mg (55 μmol) of methyl 2,5-dioxo-2,5-dihydro-1H-pyrrole-1-carboxylate were added, and the reaction mixture was adjusted again to pH 9 and stirred at RT for a further hour. This was followed by concentration and purification of the remaining residue by means of preparative HPLC. At first, 31 mg of an as yet uncyclized intermediate were obtained. 27 mg of this intermediate were taken up again in 2 ml of 1:1 dioxane/water and then admixed with 250 μl of saturated sodium hydrogencarbonate solution. After stirring at RT for 2 hours, the reaction mixture was concentrated and the residue was purified by means of preparative HPLC. After lyophilization, 20 mg (29% of theory) of the title compound were obtained.

Workup

  1. concentrationconcentrated under reduced pressure
  2. stirringstirred at RT for a further hour
  3. concentrationThis was followed by concentration and purification of the remaining residue by means of preparative HPLC
  4. customAt first, 31 mg of an as yet uncyclized intermediate were obtained
  5. stirringAfter stirring at RT for 2 hours
  6. concentrationthe reaction mixture was concentrated
  7. customthe residue was purified by means of preparative HPLC

Sources & evidence

ORD record
ord-458c6aaf16af4238813530498e0290ac
Source dataset
uspto-grants-2015_03
Patent number
US08992932B2

Reaction notes

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