Formaldehyde → HCID 89807019, compound

HRID 1400000Notes

Reaction equation

HRID 1400000 reaction equation
N(C1C=C(Br)C2SC(NC(NCC)=O)=NC=2C=1)=[N+]=[N-].C=O.CN.[N:24]([C:27]1[CH:28]=[C:29]([Br:46])[C:30]2[S:34][C:33]([N:35]3[CH2:40][N:39]([CH3:41])[CH2:38][N:37]([CH2:42][CH3:43])[C:36]3=[O:44])=[N:32][C:31]=2[CH:45]=1)=[N+:25]=[N-:26].[CH2:47]([O:49][CH:50]([O:53][CH2:54][CH3:55])[C:51]#[CH:52])[CH3:48].CCN(C(C)C)C(C)C>CO.CN(C=O)C.[Cu]I.O>[Br:46][C:29]1[C:30]2[S:34][C:33]([N:35]3[CH2:40][N:39]([CH3:41])[CH2:38][N:37]([CH2:42][CH3:43])[C:36]3=[O:44])=[N:32][C:31]=2[CH:45]=[C:27]([N:24]2[CH:52]=[C:51]([CH:50]([O:53][CH2:54][CH3:55])[O:49][CH2:47][CH3:48])[N:26]=[N:25]2)[CH:28]=1

Participants

11

Reactant 6

HCID 712FormaldehydeHCID 6329MethylamineHCID 662853,3-DiethoxypropyneHCID 81531DiisopropylethylamineHCID 89807003HCID 89807003, compoundHCID 89807198HCID 89807198, compound

Product 1

HCID 89807019HCID 89807019, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Compound i (1.68 g, 4.89 mmol) was suspended in MeOH (65 mL) and formaldehyde (37 wt % in H2O, 7.94 g, 97.9 mmol) then methylamine (2 M in MeOH, 24.5 mL, 49 mmol) added. The suspension was heated to 80° C. for 5 h. H2O was added and the mixture extracted with EtOAc and then DCM. The organic layers were dried (Na2SO4), filtrated and concentrated in vacuo to give a residue that contained 1-(5-azido-7-bromo-1,3-benzothiazol-2-yl)-3-ethyl-5-methyl-1,3,5-triazinan-2-one (1.31 g). A part of this mixture (827 mg; 2.09 mmol) was suspended in DMF (36 mL), cooled down at 0° C. and then treated with 3,3-diethoxyprop-1-yne (535 mg, 4.17 mmol), DIPEA (320 mg, 2.5 mmol) and CuI (70 mg; 0.37 mmol). The ice bath was removed and the reaction let to stir overnight at RT. The mixture was freeze-dried and the residue purified by chromatography on silica (0-5% MeOH gradient in DCM) to give a residue that was triturated with EtOAc affording ii (354 mg, 13%) 1H NMR (400 MHz, DMSO-d6) δ 8.90 (s, 1H), 8.26 (d, J=1.8 Hz, 1H), 8.10 (d, J=1.8 Hz, 1H), 5.75 (s, 1H), 5.13 (s, 2H), 4.40 (s, 2H), 3.63 (qq, J=9.6, 7.1 Hz, 4H), 3.38 (q, J=7.1 Hz, 2H), 2.55 (s, 3H), 1.18 (t, J=7.1 Hz, 6H), 1.13 (t, J=7.1 Hz, 3H).

Workup

  1. extractionthe mixture extracted with EtOAc
  2. dry with materialThe organic layers were dried (Na2SO4)
  3. filtrationfiltrated
  4. concentrationconcentrated in vacuo
  5. customto give a residue that
  6. temperaturecooled down at 0° C.
  7. customThe ice bath was removed
  8. customThe mixture was freeze-dried
  9. customthe residue purified by chromatography on silica (0-5% MeOH gradient in DCM)
  10. customto give a residue that
  11. customwas triturated with EtOAc affording ii (354 mg, 13%) 1H NMR (400 MHz, DMSO-d6) δ 8.90 (s, 1H), 8.26 (d, J=1.8 Hz, 1H), 8.10 (d, J=1.8 Hz, 1H), 5.75 (s, 1H), 5.13 (s, 2H), 4.40 (s, 2H), 3.63 (qq, J=9.6, 7.1 Hz, 4H), 3.38 (q, J=7.1 Hz, 2H), 2.55 (s, 3H), 1.18 (t, J=7.1 Hz, 6H), 1.13 (t, J=7.1 Hz, 3H)

Sources & evidence

ORD record
ord-1f920c2105634f72b32c8efed5b36bfc
Source dataset
uspto-grants-2014_12
Patent number
US08906902B2

Reaction notes

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