Phenyl thioxochloroformate → HCID 131730617, compound

HRID 1255406Notes

Reaction equation

HRID 1255406 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@@:13]([CH:23]=[CH:24][CH2:25][CH2:26][CH3:27])([CH2:14][O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:28]2[CH:36]=[C:34]([CH3:35])[C:32](=[O:33])[NH:31][C:29]2=[O:30])[C:10]1(O)[OH:37])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:39]1[CH:44]=[CH:43][C:42]([O:45][C:46](Cl)=[S:47])=[CH:41][CH:40]=1>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[CH2:1]([O:8][C@@H:9]1[C@@:13]([CH:23]=[CH:24][CH2:25][CH2:26][CH3:27])([CH2:14][O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:28]2[CH:36]=[C:34]([CH3:35])[C:32](=[O:33])[NH:31][C:29]2=[O:30])[C@@H:10]1[O:37][C:46]([O:45][C:42]1[CH:43]=[CH:44][CH:39]=[CH:40][CH:41]=1)=[S:47])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 70498Phenyl thioxochloroformateHCID 68576928HCID 68576928, compound

Product 1

HCID 131730617HCID 131730617, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

The nucleoside 20 (2.8 g, 5.7 mmol) was evaporated thrice with dry pyridine and dissolved in the same. To this pre-cooled solution was added DMAP (0.69 g, 5.7 mmol) and then dropwise was added phenyl chlorothionoformate (1.15 mL, 8.55 mmol) and reaction stirred overnight. Reaction was quenched with saturated solution of NaHCO3 and extracted with dichloromethane. Organic layer was dried over MgSO4 concentrated and chromatographed over silica gel (10-30% ethyl acetate in cyclohexane, v/v) to give 21 as yellowish foam (2.1 g, 3.42 mmol, 60%). Rf=0.60 (30% ethyl acetate in cyclohexane, v/v). 1H NMR (600 MHz, CDCl3) δ: 8.32 (1H, br s, NH), 7.48 (1H, s, H6), 7.48-6.99 (15H, m), 6.4 (1H, d, JH1′,H2′=6.3 Hz, H1′), 5.94 (1H, app t, J=6.0 Hz, H2′), 5.77 (1H, m, H8′), 4.97 (2H, m, H9′ and H9″), 4.77 (1H, d, Jgem=12 Hz, CH2Bn), 4.55 (3H, d, Jgem=12 Hz, CH2Bn), 4.53 (1H, d, JH2′,H3′=5.8 Hz, H3′), 3.74 (1H, d, JH5′,H5″=9.9 Hz, H5″), 3.47 (1H, d, JH5′,H5″=9.9 Hz, H5′), 2.22 (1H, m, H7′), 2.06 (1H, m, H7″), 1.94 (1H, m, H6′), 1.66 (1H, m, H6″), 1.53 (3H, thymine CH3); 13C NMR (125.7 MHz, CDCl3) δ: 194.4 (C═S), 163.3 (C4), 153.3, 150.2 (C2), 138.1 (C8′), 137.3, 137.0, 135.6 (C6), 129.5-121.9 (aromatic), 114.8 (C9′), 111.5 (C5), 87.6 (C4′), 85.1 (C1′), 82.9 (C2′), 78.1 (C3′), 74.9 (CH2Bn), 73.7 (C5′), 73.6 (CH2Bn), 31.6 (C6′), 27.6 (C7′), 12.0 (CH3 thymine); MALDI-TOF m/z [M+H]+ found 629.09, calcd 629.73.

Workup

  1. dissolutiondissolved in the same
  2. additiondropwise was added
  3. customReaction
  4. customwas quenched with saturated solution of NaHCO3
  5. extractionextracted with dichloromethane
  6. dry with materialOrganic layer was dried over MgSO4
  7. concentrationconcentrated
  8. customchromatographed over silica gel (10-30% ethyl acetate in cyclohexane, v/v)

Sources & evidence

ORD record
ord-fabe0ef7eb984ec09d27336d7be8b574
Source dataset
uspto-grants-2013_06
Patent number
US08461124B2

Reaction notes

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