Water → HCID 67264575, compound

HRID 1688012Notes

Reaction equation

HRID 1688012 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-b4cc35209b654733b09dfb4700df95d4
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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