Ammonia → HCID 87504037, compound

HRID 1255405Notes

Reaction equation

HRID 1255405 reaction equation
[CH2:1]([C@:4]1([CH2:30][O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[O:8][C@@H:7]([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[C@H:6]([O:18]C(=O)C)[C@@H:5]1[O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:2]=[CH2:3].N.[CH:40]1[CH:45]=[CH:44][C:43]([O:46][C:47](Cl)=[S:48])=[CH:42][CH:41]=1>CN(C1C=CN=CC=1)C>[CH2:1]([C@:4]1([CH2:30][O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[O:8][C@@H:7]([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[C@H:6]([O:18][C:47]([O:46][C:43]2[CH:44]=[CH:45][CH:40]=[CH:41][CH:42]=2)=[S:48])[C@@H:5]1[O:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 70498Phenyl thioxochloroformateHCID 68577213HCID 68577213, compound

Product 1

HCID 87504037HCID 87504037, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

Compound 8 (5.0 g, 9.6 mmol) was treated with 27% methanolic ammonia solution overnight. After evaporation of the solvent the crude was coevaporated thrice with dry pyridine and dissolved in the same. To this pre-cooled solution was added DMAP (1.17 g, 9.6 mmol) and then dropwise was added phenyl chlorothionoformate (1.6 mL, 11.53 mmol) and reaction stirred overnight. Reaction was quenched with saturated solution of NaHCO3 and extracted with dichloromethane. The organic layer was dried over MgSO4, concentrated and chromatographed over silica gel (10-30% ethyl acetate in cyclohexane, v/v) to give 10 as yellowish foam (4.1 g, 6.72 mmol, 70%). Rf=0.60 (30% ethyl acetate in cyclohexane, v/v). 1H NMR (600 MHz) δ: 8.58 (1H, s, N—H), 7.48 (1H, s, H6), 7.19 (15H, m), 6.44 (1H, d, JH1′,H2′=6.1 Hz, H1′), 5.97 (1H, app t, J=5.8 Hz, H2′), 5.83 (1H, m, H7′), 5.09 (2H, m, H8′-H8″), 4.77 (1H, d, Jgem=11.2 Hz, CH2Bn), 4.55 (3H, m, CH2Bn, H3′), 3.71 (1H, d, JH5′,H5″=10.3 Hz, H5″), 3.48 (1H, d, JH5′,H5″10.3 Hz, H5′), 2.66 (1H, dd, JH6,H6=14.6 Hz, JH6,H7=8.1 Hz, H6″), 2.35 (1H, dd, JH6,H6=14.6 Hz, JH6,H7=8.1 Hz, H6′), 1.51 (3H, CH3, thymine); 13C NMR (125.7 MHz) δ: 194.4 (>C═S), 163.4 (C4), 150.3 (C2), 137.1, 137.2 (aromatic), 135.6 (C6), 132.4 (C7′), 121.6, 126.7, 127.3, 127.6, 127.8, 128.0, 128.1, 128.4, 128.6, 129.3, 129.5 (aromatic), 118.8 (C8′), 111.5 (C5′), 87.1 (C4′), 85.1 (C2′), 82.9 (C1′), 77.8 (C3′), 74.9 (C—CH2Bn), 73.7 (C5′), 73.7 (C—CH2Bn), 37.3 (C6′), 11.9 (CH3, thymine); MALDI-TOF m/z [M+H]+ found 615.16 calcd 615.21.

Workup

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

Sources & evidence

ORD record
ord-82397a20951d46f68a3e2a9814a2f702
Source dataset
uspto-grants-2013_06
Patent number
US08461124B2

Reaction notes

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