Tetrahydrofuran → (1S,2R,3R)-3-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexane-1,2-diol

HRID 1848265Notes

Reaction equation

HRID 1848265 reaction equation
C[N+]1([O-])CC[O:5]CC1.[C@@H:9]1([NH:15][C:16]2[S:17][C:18]3[CH:24]=[C:23]([CH2:25][N:26]4[C:30]5=[N:31][CH:32]=[C:33]([F:35])[CH:34]=[C:29]5[N:28]=[CH:27]4)[CH:22]=[CH:21][C:19]=3[N:20]=2)CCCC=[CH:10]1.[CH2:36]1[CH2:40][O:39][CH2:38][CH2:37]1>C(O)(C)(C)C.O.O=[Os](=O)(=O)=O>[F:35][C:33]1[CH:34]=[C:29]2[N:28]=[CH:27][N:26]([CH2:25][C:23]3[CH:22]=[CH:21][C:19]4[N:20]=[C:16]([NH:15][C@@H:9]5[CH2:10][CH2:38][CH2:37][C@H:36]([OH:5])[C@@H:40]5[OH:39])[S:17][C:18]=4[CH:24]=3)[C:30]2=[N:31][CH:32]=1

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 82029Methyl morpholine oxideHCID 86681194(R)-N-(cyclohex-2-en-1-yl)-6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-amine

Product 1

HCID 86681238(1S,2R,3R)-3-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexane-1,2-diolYield 2%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent2×HCID 6386tert-ButanolSolvent

Procedure

To a stirred mixture of NMO in tert-butanol (5 mL), THF (1.5 mL), H2O (0.5 mL), and a 4% wt solution of OsO4 in H2O (10 μL, 0.3 mmol) at rt was added portionwise (R)—N-(cyclohex-2-en-1-yl)-6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-amine (142 mg, 0.4 mmol) from Example 176. After the mixture was stirred at rt for 18 h, it was partitioned between EtOAc (200 mL) and 0.5 M aq K2CO3 (100 mL). The organic layer was separated, washed with brine (100 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified twice by reverse-phase preparative HPLC eluting with a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford (1S,2R,3R)-3-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexane-1,2-diol (7 mg, 2%) as a white powder. 1H NMR (500 MHz, DMSO-d6) δ 8.67 (s, 1H), 8.40 (m, 1H), 8.07 (dd, J=2.6, 9.5 Hz, 1H), 7.95 (d, J=7.9 Hz, 1H), 7.66 (d, J=1.2 Hz, 1H), 7.29 (d, J=8.4 Hz, 1H), 7.21 (dd, J=1.6, 8.2 Hz, 1H), 5.47 (s, 2H), 4.45-4.70 (m, 2H), 3.88 (br s, 1H), 3.76 (m, 1H), 3.43 (m, 1H), 1.40-1.62 (m, 5H), 1.25 (m, 1H); LCMS (ESI) m/z 414 (M+H)+.

Workup

  1. customit was partitioned between EtOAc (200 mL) and 0.5 M aq K2CO3 (100 mL)
  2. customThe organic layer was separated
  3. washwashed with brine (100 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified twice by reverse-phase preparative HPLC
  8. washeluting with a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase

Sources & evidence

ORD record
ord-caf27a93e0bf4b1eb0c714812b97c8e9
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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