Lithium Chloride → HCID 136983547, compound

HRID 929218Notes

Reaction equation

HRID 929218 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[NH:26][C:25]([O:27][CH:28]3[CH:32]4[O:33][CH2:34][C@H:35]([OH:36])[CH:31]4[O:30][CH2:29]3)=[N:24][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[C:15]=2[O:22]C)=[CH:10][CH:9]=1.[Cl-].[Li+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:26][C:25]([O:27][CH:28]3[CH:32]4[O:33][CH2:34][C@H:35]([OH:36])[CH:31]4[O:30][CH2:29]3)=[N:24][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[C:15]=2[OH:22])=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 433294Lithium ChlorideHCID 90041622HCID 90041622, compound

Product 1

HCID 136983547HCID 136983547, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of (3S)-6-[[6-chloro-5-[4-(3,5-difluoro-2-methoxy-phenyl)phenyl]-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (5.2 mg, 0.01 mmol), and lithium chloride (45.0 mg, 1.06 mmol) in DMF (0.5 mL) was heated in a 140° C. oil bath for 20 hours and then 3.5 additional hours at 150° C. The reaction mixture was cooled to room temperature and purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column eluting with a 20%-100% acetonitrile/water+0.05% TFA gradient followed by a 100% acetonitrile/water+0.05% TFA flush. The desired fractions were combined, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give the title compound as a light yellow solid. LC-MS: calculated for C24H18ClF2N3O5 501.09 observed m/e: 502.13 (M+H)+ (Rt 1.16/2 min); 1H NMR δ (ppm) (CD3OD): 7.83 (s, 1H), 7.66-7.74 (m, 4H), 6.93-6.98 (m, 2H), 5.55 (qt, 1H), 4.97 (t, 1H), 4.47 (t, 1H), 4.26-4.30 (m, 1H), 4.17 (dd, 1H), 4.11 (dd, 1H), 3.90 (t, 1H), 3.60 (t, 1H).

Workup

  1. customat 150° C
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompurified by preparative HPLC reverse phase (C-18)
  4. washeluting with a 20%-100% acetonitrile/water+0.05% TFA
  5. customflush
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-5cec26f0ecd0415b8bf8228f5996b3e2
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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