Triethylamine → HCID 86684716, compound

HRID 1057228Notes

Reaction equation

HRID 1057228 reaction equation
C(C1C=C(C(C)C)C=C(C(C)C)C=1S(Cl)(=O)=O)(C)C.[Si:20]([C@@:27]1([OH:67])[C@@H:31]([CH2:32][O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[O:30][C@@H:29]([N:41]2[CH:48]=[C:47]([CH2:49][O:50][C@H:51]([C:56]3[CH:61]=[C:60]([O:62][CH3:63])[CH:59]=[CH:58][C:57]=3[N+:64]([O-:66])=[O:65])[C:52]([CH3:55])([CH3:54])[CH3:53])[C:45](=O)[NH:44][C:42]2=[O:43])[CH2:28]1)([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21].C([N:70](CC)CC)C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Si:20]([C@@:27]1([OH:67])[C@@H:31]([CH2:32][O:33][Si:34]([C:37]([CH3:39])([CH3:40])[CH3:38])([CH3:36])[CH3:35])[O:30][C@@H:29]([N:41]2[CH:48]=[C:47]([CH2:49][O:50][C@H:51]([C:56]3[CH:61]=[C:60]([O:62][CH3:63])[CH:59]=[CH:58][C:57]=3[N+:64]([O-:66])=[O:65])[C:52]([CH3:53])([CH3:55])[CH3:54])[C:45]([NH2:70])=[N:44][C:42]2=[O:43])[CH2:28]1)([C:23]([CH3:25])([CH3:24])[CH3:26])([CH3:22])[CH3:21]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 810422,4,6-Tris(1-methylethyl)benzenesulfonyl chlorideHCID 89558187HCID 89558187, compound

Product 1

HCID 86684716HCID 86684716, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

2,4,6-Triisopropyl benzenesulfonyl chloride (363 mg, 1.2 mmol) was added to a solution of compound 48 (170 mg, 0.24 mmol), DMAP (32 mg, 0.26 mmol), and triethylamine (0.34 mL, 2.4 mmol) in anhydrous CH2Cl2 (8.0 mL). The mixture was stirred at room temperature overnight under a nitrogen atmosphere, concentrated in vacuo, and the residue was dissolved in a solution of NH3 in 1,4-dioxane (0.5 M, 20 mL). The mixture was transferred into a sealed tube and was heated at 90° C. overnight. The mixture was cooled to room temperature, concentrated in vacuo, dissolved in CH2Cl2 (20 mL), and washed with brine (50 mL). The organic and aqueous phases were separated, and the aqueous phase was extracted with CH2Cl2 (30 mL) three times. The combined organic phase was dried over Na2SO4, concentrated in vacuo, and the residue was purified by silica gel column chromatography to yield 3′,5′-O-bis-(tert-butyldimethylsilyl)-5-[(S)-1-(5-methoxy-2-nitrophenyl)-2,2-dimethyl-propyloxy]methyl-2′-deoxycytidine 49 (110 mg, 65% for two steps). 1H NMR (400 MHz, DMSO-d6): δ 7.96 (d, J=8.8 Hz, 1H, Ph-H), 7.50 (br s, 1H, NH2), 7.38 (s, 1H, H-6), 7.08 (dd, 1H, J=2.8 and 8.8 Hz, Ph-H), 7.04 (d, 1H, J=2.8 Hz, Ph-H), 6.80 (br s, 1H, NH2), 6.13 (t, 1H, J=6.4 Hz, H-1′), 5.09 (s, 1H, Ph-CH), 4.31 (m, 1H, H-3′), 4.25 (d, 1H, J=12.8 Hz, 5-CH2a), 4.08 (d, 1H, J=12.8 Hz, 5-CH2b), 3.87 (s, 3H, OCH3), 3.76 (m, 1H, H-4′), 3.64 (m, 2H, H-5′), 3.76 (dd, 1H, J=2.8 Hz, H-5′b), 2.10 (m, 1H, H-2′a), 2.00 (m, 1H, H-2′b), 0.87 (s, 9H, C(CH3)3), 0.78 and 0.76 (2 s, 18H, SiC(CH3)3), 0.07, 0.06, −0.01, and −0.04 (4 s, 12H, SiCH3).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionthe residue was dissolved in a solution of NH3 in 1,4-dioxane (0.5 M, 20 mL)
  3. customThe mixture was transferred into a sealed tube
  4. temperaturewas heated at 90° C. overnight
  5. temperatureThe mixture was cooled to room temperature
  6. concentrationconcentrated in vacuo
  7. dissolutiondissolved in CH2Cl2 (20 mL)
  8. washwashed with brine (50 mL)
  9. customThe organic and aqueous phases were separated
  10. extractionthe aqueous phase was extracted with CH2Cl2 (30 mL) three times
  11. dry with materialThe combined organic phase was dried over Na2SO4
  12. concentrationconcentrated in vacuo
  13. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a6f5fb64e9444507afa72d8f516d08a6
Source dataset
uspto-grants-2016_07
Patent number
US09399798B2

Reaction notes

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