Water → HCID 71062432, compound

HRID 528982Notes

Reaction equation

HRID 528982 reaction equation
C(O[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15]([CH2:16][CH2:17][CH2:18][CH3:19])=[C:14]([C:20]3[CH:41]=[CH:40][C:23]([C:24]([NH:26][S:27]([C:30]4[CH:39]=[CH:38][C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[CH:31]=4)(=[O:29])=[O:28])=[O:25])=[CH:22][C:21]=3[C:42]([N:44]3[CH2:53][CH2:52][C:51]4[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=4)[CH2:45]3)=[O:43])[C:13]([CH2:54][OH:55])=[N:12]2)=[CH:7][CH:6]=1)C=C.[OH2:56].C[N+]1([O-])CC[O:61]CC1.[C:65]([OH:69])(C)([CH3:67])[CH3:66]>C1COCC1.CCOC(C)=O.[Os](=O)(=O)(=O)=O>[CH2:16]([C:15]1[N:11]([C:8]2[CH:7]=[CH:6][C:5]([O:56][CH2:66][CH:65]([OH:69])[CH2:67][OH:61])=[CH:10][CH:9]=2)[N:12]=[C:13]([CH2:54][OH:55])[C:14]=1[C:20]1[CH:41]=[CH:40][C:23]([C:24]([NH:26][S:27]([C:30]2[CH:39]=[CH:38][C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH:31]=2)(=[O:29])=[O:28])=[O:25])=[CH:22][C:21]=1[C:42]([N:44]1[CH2:53][CH2:52][C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH2:45]1)=[O:43])[CH2:17][CH2:18][CH3:19]

Participants

8

Reactant 4

HCID 962WaterHCID 6386tert-ButanolHCID 82029Methyl morpholine oxideHCID 86718927HCID 86718927, compound

Product 1

HCID 71062432HCID 71062432, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(1-(4-(allyloxy)phenyl)-5-butyl-3-(hydroxymethyl)-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (Example 246, 30 mg, 0.040 mmol) in tert-BuOH (1 mL), THF (0.3 mL), and water (0.1 mL) at 0° C. was added NMO (5.6 mg, 0.048 mmol) followed by osmium tetroxide (0.062 mL, 7.9 mmol, 4 wt %). After stirring at room temperature overnight, the reaction mixture was diluted with EtOAc, washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography (Isco 40 g column eluting with 0-15% methanol/DCM). The resulting solid was lyophilized from acetonitrile/water to give the title compound (22 mg, 70%) as a white solid. 1H NMR (CD3OD, 1:1 mixture of amide rotamers) δ 8.62 (s, 1H), 8.14-7.93 (m, 6H), 7.64-7.57 (m, 2H), 7.40-6.87 (m, 9H), 4.87-4.00 (m, 9H), 3.70-3.67 (m, 2H), 3.12-2.35 (m, 4H), 1.07-0.88 (m, 4H), 0.56-0.52 (m, 3H); MS(ESI+) m/z 789.5 (M+H).

Workup

  1. washwashed with brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography (Isco 40 g column eluting with 0-15% methanol/DCM)

Sources & evidence

ORD record
ord-74d7389b28ae4c37b3498d36d2981b1d
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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