Hydrochloric Acid → HCID 57520839, compound

HRID 595372Notes

Reaction equation

HRID 595372 reaction equation
N1(C(=S)[O-])C=CN=C1.CCCC[SnH](CCCC)CCCC.C1CCC(N=NC2(C#N)CCCCC2)(C#N)CC1.[CH3:40][N:41]([CH3:61])[C:42]1[S:43][C@H:44]2[O:50][C@@H:49]3[CH2:51][O:52]C(C4C=CC=CC=4)[O:54][C@H:48]3[CH2:47][C@H:45]2[N:46]=1.Cl>CN(C=O)C.C1COCC1.CO>[OH:52][CH2:51][C@H:49]1[O:50][C@H:44]2[C@H:45]([N:46]=[C:42]([N:41]([CH3:40])[CH3:61])[S:43]2)[CH2:47][C@@H:48]1[OH:54]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 5948TributylstannaneHCID 749781,1'-Azobis(cyclohexanecarbonitrile)HCID 67982769HCID 67982769, compoundHCID 178526208HCID 178526208, compound

Product 1

HCID 57520839HCID 57520839, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of the above material (0.67 g, 2.0 mmol) and thio-CDI (90% tech, 1.6 g, 8.0 mmol) in anhydrous DMF (20 mL) was stirred at 95° C. overnight. After cooling the solvent was removed under reduced pressure, and the residue was purified on silica gel by flash column chromatography (MeOH/DCM, 1:100 to 5:100), affording a mixture containing O-(-(3aR,4aR,8aS,9R,9aR)-2-(dimethylamino)-7-phenyl-3a,4a,5,8a,9,9a-hexahydro-[1,3]dioxino[4′,5′:5,6]pyrano[3,2-d]thiazol-9-yl) 1H-imidazole-1-carbothioate. This mixture was dissolved in anhydrous THF (30 mL), and Bu3SnH (1.0 g, 3.4 mmol) and ABCN (0.060 mg, 0.24 mmol) was added, and the mixture was stirred at reflux overnight. The solvent was then removed under reduced pressure, and the residue was purified on silica gel by flash column chromatography (1.0 M NH3 in MeOH:DCM, 3:100), affording an pale yellow solid containing -(3aR,4aR,8aS,9aR)-N,N-dimethyl-7-phenyl-3a,4a,5,8a,9,9a-hexahydro-[1,3]dioxino[4′,5′:5,6]pyrano[3,2-d]thiazol-2-amine (0.17 g, impure). The solid was treated with 2% HCl in MeOH (10 mL) at room temperature for 2 h, and then the solvent was removed under reduced pressure. The residue was neutralized with 1.0 M NH3 in MeOH, and subsequently purified on silica gel by flash column chromatography (1.0 M NH3 in MeOH:DCM, 1:10), affording pure -(3aR,5R,6S,7aR)-5-(hydroxymethyl)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-6-ol as an off-white solid (0.050 g, 11% overall yield). 1H NMR (400 MHz, CD3OD) δ 6.23 (d, J=6.4 Hz, 1H), 4.28-4.24 (m, 1H), 3.74 (dd, J=2.5, 12.0 Hz, 1H), 3.70-3.65 (m, 1H), 3.59 (dd, J=6.2, 12.0 Hz, 1H), 3.53-3.48 (m, 1H), 2.99 (s, 6H), 2.14-2.08 (m, 1H), 2.02-1.95 (m, 1H); 13C NMR (100 MHz, CD3OD) δ 165.60, 92.43, 77.19, 69.67, 65.79, 63.27, 40.15, 34.93; MS, m/z=255 (M+23).

Workup

  1. temperatureAfter cooling the solvent
  2. customwas removed under reduced pressure
  3. customthe residue was purified on silica gel by flash column chromatography (MeOH/DCM, 1:100 to 5:100)
  4. customaffording a mixture
  5. stirringthe mixture was stirred
  6. temperatureat reflux overnight
  7. customThe solvent was then removed under reduced pressure
  8. customthe residue was purified on silica gel by flash column chromatography (1.0 M NH3 in MeOH:DCM, 3:100)
  9. customaffording an pale yellow solid
  10. customthe solvent was removed under reduced pressure
  11. customsubsequently purified on silica gel by flash column chromatography (1.0 M NH3 in MeOH:DCM, 1:10)
  12. customaffording pure -

Sources & evidence

ORD record
ord-33620f15b793437fb36d657c3c819143
Source dataset
uspto-grants-2016_01
Patent number
US09243020B2

Reaction notes

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