Methanol → HCID 87970440, compound

HRID 989619Notes

Reaction equation

HRID 989619 reaction equation
[Si:1]([O:8][CH2:9][C@@H:10]1[O:14][C@H:13]([N:15]2[CH:22]=[C:21]([F:23])[C:19]([NH2:20])=[N:18][C:16]2=[O:17])[C@H:12]([OH:24])[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:25][S:26](Cl)(=[O:28])=[O:27].CO>N1C=CC=CC=1.C1(C)C=CC=CC=1>[S:26]([O:24][C@@H:12]1[CH2:11][C@H:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3])[O:14][C@@H:13]1[N:15]1[CH:22]=[C:21]([F:23])[C:19]([NH2:20])=[N:18][C:16]1=[O:17])([CH3:25])(=[O:28])=[O:27]

Participants

6

Reactant 3

HCID 887MethanolHCID 31297Methanesulfonyl chlorideHCID 69541951HCID 69541951, compound

Product 1

HCID 87970440HCID 87970440, compoundYield 68.1%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 19 (1.70 g, 4.73 mmol) in dry pyridine (80 mL) was stirred under argon and cooled to 0° C. Methanesulfonyl chloride (MsCl, 1.21 mL, 15.6 mmol) was added dropwise and the reaction mixture stirred at 0° C. for 5 h. Then the mixture was poured onto ice/water (300 mL) and extracted with chloroform (3×300 mL). Combined extracts were washed with a 5% aqueous sodium hydrogen carbonate solution (300 mL), with water (2×300 mL) and then dried over sodium sulphate and evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography [eluent: stepwise gradient of methanol (8-12%) in toluene] to give pure 20 (1.41 g, 68% yield) as a white solid: mp 75-76 ° C.; UV (ethanol): λmax 243 nm (ε8100), 282 nm (ε7300), λmin 225 nm (ε6000), 265 nm (ε6000); 1H NMR (DMSO-d6): δ7.9-7.6 (br d, 2H, NH2), 7.85 (d, 1H, H-6, J6-F5=7.0 Hz), 6.08 (dd, 1H, H-1′, J1′-2′=5.2 Hz and J1′-F5=1.6 Hz), 5.4 (m, 1H, H-2′), 4.1 (m, 1H, H-4′), 3.9 (m, 1H, H-5′), 3.7 (m, 1H, H-5″), 3.11 (s, 3H, CH3SO2), 2.47 (m, 1H, H-3′), 2.0 (m, 1H, H-2″), 0.85 (s, 9H, (CH3)3C—Si), 0.05 (s, 6H, (CH3)2Si); MS (matrix GT): FAB>0 m/z 1312 (3M+H)+, 875 (2M+H)+, 438 (M+H)+, 309 (S)+, 130 (BH2)+; FAB<0 m/z 1310 (2M−H)−, 873 (2M−H)−, 436 (M−H)−, 128 (B)−, 95 (CH3SO3)−; [α]D20=−84 (c, 0.84 DMSO).

Workup

  1. stirringthe reaction mixture stirred at 0° C. for 5 h
  2. additionThen the mixture was poured onto ice/water (300 mL)
  3. extractionextracted with chloroform (3×300 mL)
  4. washCombined extracts were washed with a 5% aqueous sodium hydrogen carbonate solution (300 mL), with water (2×300 mL)
  5. dry with materialdried over sodium sulphate
  6. customevaporated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography [eluent

Sources & evidence

ORD record
ord-97a0b0660fc044e2b18878bfe67c7dca
Source dataset
uspto-grants-2002_10
Patent number
US06458773B1

Reaction notes

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