Water → HCID 25125062, compound

HRID 2038575Notes

Reaction equation

HRID 2038575 reaction equation
C1([N:6]([C@@H:10]([C:44]([CH3:47])([CH3:46])[CH3:45])[C:11]([N:13]2[C@H:17]([C:18](=[O:32])[NH:19][CH:20]([CH2:29][CH2:30][CH3:31])[C@H:21]([OH:28])[C:22]([NH:24][CH:25]3[CH2:27][CH2:26]3)=[O:23])[CH2:16][C@@:15]3([CH2:36][C:35](=[O:37])[N:34]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[CH2:33]3)[CH2:14]2)=[O:12])[C:7](=O)[O-:8])CCCC1.O[NH-].CC(OI1(OC(C)=O)(OC(C)=O)O[C:61](=O)[C:60]2[CH:59]=[CH:58][CH:57]=CC1=2)=O.S([O-])([O-])(=O)=S.[Na+].[Na+].[OH2:79]>C(Cl)Cl>[CH:57]1([O:79][C:7](=[O:8])[NH:6][C@@H:10]([C:44]([CH3:47])([CH3:46])[CH3:45])[C:11]([N:13]2[C@H:17]([C:18](=[O:32])[NH:19][C@@H:20]([CH2:29][CH2:30][CH3:31])[C:21](=[O:28])[C:22]([NH:24][CH:25]3[CH2:27][CH2:26]3)=[O:23])[CH2:16][C@@:15]3([CH2:36][C:35](=[O:37])[N:34]([C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=4)[CH2:33]3)[CH2:14]2)=[O:12])[CH2:58][CH2:59][CH2:60][CH2:61]1

Participants

6

Reactant 4

HCID 962WaterHCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 178449504HCID 178449504, compound

Product 1

HCID 25125062HCID 25125062, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The hydroxy amide cyclopentyl-(S)-1-((3S,5R)-3-((S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-ylcarbamoyl)-8-oxo-7-phenyl-2,7-diazaspiro[4.4]nonan-2-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (J6a) (4.1 mg, 6.3 μmol) was dissolved in CH2Cl2 (1.0 ml) and treated with Dess-Martin periodinane (DMP, 8.0 mg, 18.9 μmol, 3 eq) for 3 hrs at room temp. The reaction was quenched with 1M sodium thiosulfate in water (32 μl, 5 eq). The reaction was loaded onto silica (eluted with ethyl acetate/hexane gradient) to give cyclopentyl-(S)-1-((3S,5R)-3-((S)-1-(cyclopropylamino)-1,2-dioxohexan-3-ylcarbamoyl)-8-oxo-7-phenyl-2,7-diazaspiro[4.4]nonan-2-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (compound no. 1) (3.1 mg, 4.8 μmol) as a white solid. NMR (CDCl3) δ5195m, 46H), 1.96 (m, 1H), 2.25 (m, 1H), 2.61 (m, 2H), 2.80 (s, 2H), 3.60 (dd, 2H), 4.00 (d, 1H), 4.22 (m, 2H), 4.70 (m, 1H), 4.90 (m, 1H), 5.20 (d, 1H), 5.35 (m, 1H), 6.90 (s, 1H), 7.19 (m, 1H), 7.38 (m, 2H), 7.65 (d, 1H). LCMS for C35H49N5O7 651.36 [M], found ES+ 652.5 [M+H]+ and ES− 650.6 [M−H]−, at 3.2 minutes retention time, using 10-90% acetonitrile/water (with 0.1% formic acid buffer) gradient over 5 minutes. The minor diastereomer cyclopentyl (S)-1-((3S,5S)-3-((S)-1-(cyclopropylamino)-1,2-dioxohexan-3-ylcarbamoyl)-8-oxo-7-phenyl-2,7-diazaspiro[4.4]nonan-2-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (compound no. 4) (1.4 mg, 2 pimp was obtained in similar fashion. 1H NMR (CDCl3) δ0.52 (m, 2H), 71m, 14H), 1.0-2.0 (m, 22H), 2.10 (m, 1H), 2.45-2.75 (m, 4H), 3.64 (t, 2H), 3.90 (d, 2H), 4.15 (d, 1H), 4.60 (m, 1H), 5.00 (m, 1H), 5.13 (d, 1H), 5.25 (m, 1H), 6.80 (m, 1H), 7.10 (m, 2H), 7.30 (m, 4H), 7.50 (m, 2H), 7.90 (m, 1H); LCMS for C35H49N5O7 651.36 [M], found ES+652.5 [M+H]+ and ES− 650.6 [M−H]−, at 3.2 minutes retention time, using 10-90% acetonitrile/water (with 0.1% formic acid buffer) gradient over 5 minutes.

Sources & evidence

ORD record
ord-522139d2077c48ecb0d3cb84f670eaac
Source dataset
uspto-grants-2013_11
Patent number
US08575208B2

Reaction notes

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