Water → HCID 67264575, compound

HRID 1041670Notes

Reaction equation

HRID 1041670 reaction equation
[Cl:1][C:2]1[C:3]([NH:25][C@@H:26]2[C@@H:31]3[CH2:32][C@@H:28]([CH:29]=[CH:30]3)[C@@H:27]2[C:33]([NH2:35])=[O:34])=[N:4][C:5]([NH:8][C:9]2[CH:22]=[CH:21][C:12]3[N:13]([CH2:19][CH3:20])[C:14](=[O:18])[CH2:15][CH2:16][CH2:17][C:11]=3[C:10]=2[O:23][CH3:24])=[N:6][CH:7]=1.[OH2:36].C[N+]1([O-])CCOCC1.[OH2:45]>CC(C)=O.C(Cl)Cl.[Os](=O)(=O)(=O)=O>[Cl:1][C:2]1[C:3]([NH:25][C@@H:26]2[C@@H:31]3[CH2:32][C@@H:28]([C@@H:29]([OH:45])[C@H:30]3[OH:36])[C@@H:27]2[C:33]([NH2:35])=[O:34])=[N:4][C:5]([NH:8][C:9]2[CH:22]=[CH:21][C:12]3[N:13]([CH2:19][CH3:20])[C:14](=[O:18])[CH2:15][CH2:16][CH2:17][C:11]=3[C:10]=2[O:23][CH3:24])=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 962Water2×HCID 2724197N-Methylmorpholine N-oxide monohydrateHCID 25229528HCID 25229528, compound

Product 1

HCID 67264575HCID 67264575, compoundYield 67%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Procedure

0.16 M of Osmium tetraoxide in Water (50 uL) was added to (1S,2S,3R,4R)-3-[5-Chloro-2-(1-ethyl-6-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (152 mg, 0.306 mmol) and 4-Methyl-morpholine 4-oxide hydrate (65 mg, 0.48 mmol) in Acetone (10 mL) and Water (1.0 mL), and the reaction was stirred under an atmosphere of Nitrogen for 45 min. The reaction was diluted with DCM (15 mL) washed with water (2×5 mL) and brine (10 mL), dried over sodium sulfate and conc. in vacuo. Chromatography of the residue (ISCO 12 g SiO2, 0-10% MeOH:DCM) afforded (1R,2S,3R,4S,5S,6R)-3-[5-Chloro-2-(1-ethyl-6-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-5,6-dihydroxy-bicyclo[2.2.1]heptane-2-carboxylic acid amide as brown solids (110 mg, 67%). MP: 164-170° C.; LCMS: 531 (M+H); 1H-NMR (CDCl3): 8.40 (d, 1H, J=8.8 Hz), 7.92 (s, 1H), 7.38 (s, 1H), 7.16 (d, 1H, J=7.8 Hz), 7.01 (d, 1H, J=9.0 Hz), 5.73 (s, 1H), 5.37 (s, 1H), 4.32 (t, 1H, J=8.0 Hz), 3.97 (m, 1H), 3.83 (m, 1H), 3.80 (s, 3H), 3.49 (d, 1H, J=5.3 Hz), 2.98 (m, 2H), 2.51 (m, 1H), 2.44 (m, 1H), 2.39 (m, 1H), 2.28 (m, 3H), 2.06 (m, 1H), 1.91 (m, 1H), 1.12 (t, 3H, J=7.2 Hz).

Workup

  1. washwashed with water (2×5 mL) and brine (10 mL)
  2. dry with materialdried over sodium sulfate and conc. in vacuo

Sources & evidence

ORD record
ord-a7832dc020574835bb130a8a3d559f71
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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