Hydrochloric Acid → HCID 71506752, compound

HRID 2406269Notes

Reaction equation

HRID 2406269 reaction equation
[S:1](=[O:32])(=[O:31])([O:3][CH2:4][C@@H:5]1[CH2:9][C@@H:8]([O:10][C:11]2[CH:16]=[C:15]([NH:17][C@@H:18]3[C:26]4[C:21](=[CH:22][C:23]([Cl:27])=[CH:24][CH:25]=4)[CH2:20][C@@H:19]3[O:28][CH3:29])[N:14]=[CH:13][N:12]=2)[CH2:7][C@@H:6]1[OH:30])[NH2:2].C(#N)C.Cl>C(OCC)C>[ClH:27].[S:1](=[O:31])(=[O:32])([O:3][CH2:4][C@@H:5]1[CH2:9][C@@H:8]([O:10][C:11]2[CH:16]=[C:15]([NH:17][C@@H:18]3[C:26]4[C:21](=[CH:22][C:23]([Cl:27])=[CH:24][CH:25]=4)[CH2:20][C@@H:19]3[O:28][CH3:29])[N:14]=[CH:13][N:12]=2)[CH2:7][C@@H:6]1[OH:30])[NH2:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 71506753HCID 71506753, compound

Product 1

HCID 71506752HCID 71506752, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

{(1S,2S,4R)-4-[(6-{[(1R,2S)-5-chloro-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]-2-hydroxycyclopentyl}methyl sulfamate 1-216 (4.44 g, 0.00916 mol) was placed in a 250-ml round bottomed flask equipped with a stir bar. Acetonitrile (82.5 mL) was added with stirring. The mixture was stirred and sonicated for several minutes (the solids did not fully dissolve). The flask was immersed in an ice bath and then, with stirring, aqueous hydrochloric acid (6.0M, 1.69 mL, 0.0101 mol) was added in a slow stream during which time the solids partially dissolved. The ice bath was removed and the reaction mixture was stirred at room temperature under an atmosphere of nitrogen for 2 hours during which time a dense white precipitate formed. Diethyl ether (82.5 mL) was added with stirring and the resulting mixture was stored in a refrigerator overnight. The precipitated product was collected on a fritted funnel, washed with cold ether, then dried for 24 hours at 42° C. under high vacuum to afford the title compound as a fluffy white powder, 3.84 g (80% yield). LCMS: formic acid, [M+H+]=485.2. 1H NMR (400 MHz, MeOD) δ 8.42 (s, 1H), 7.30 (s, 1H), 7.27-7.18 (m, 2H), 6.26 (s, 1H), 5.78 (s, 1H), 5.30 (s, 1H), 4.46-4.38 (td, J=5.2, 2.0 Hz, 1H), 4.39-4.25 (m, 2H), 4.23-4.13 (dd, J=9.9, 7.4 Hz, 1H), 3.37 (s, 3H), 3.18-3.04 (m, 2H), 2.62-2.47 (m, 1H), 2.42-2.31 (ddd, J=15.0, 6.9, 2.0 Hz, 1H), 2.24-2.14 (dt, J=15.0, 4.6 Hz, 1H), 2.14-2.02 (dd, J=10.3, 5.9 Hz, 2H).

Workup

  1. customequipped with a stir bar
  2. stirringThe mixture was stirred
  3. customsonicated for several minutes (the solids
  4. dissolutiondid not fully dissolve)
  5. customThe flask was immersed in an ice bath
  6. stirringwith stirring
  7. dissolutionpartially dissolved
  8. customThe ice bath was removed
  9. stirringthe reaction mixture was stirred at room temperature under an atmosphere of nitrogen for 2 hours during which time a dense white precipitate
  10. customformed
  11. stirringwith stirring
  12. customwas stored in a refrigerator overnight
  13. customThe precipitated product was collected on a fritted funnel
  14. washwashed with cold ether
  15. customdried for 24 hours at 42° C. under high vacuum

Sources & evidence

ORD record
ord-546c71f6221e47519cd2caf53b0b8e04
Source dataset
uspto-grants-2014_08
Patent number
US08809356B2

Reaction notes

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