Dichloromethane → HCID 178484231, compound

HRID 424526Notes

Reaction equation

HRID 424526 reaction equation
[CH3:1][N:2]([CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][S:16][C:15]2[CH:19]=[C:20]([NH:23][C:24]([C:26]3[S:27][CH:28]=[CH:29][CH:30]=3)=[NH:25])[CH:21]=[CH:22][C:14]1=2)[CH2:3][C:4]([O:6]C(C)(C)C)=[O:5].C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O.C(Cl)[Cl:47]>>[ClH:47].[ClH:47].[CH3:1][N:2]([CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][S:16][C:15]2[CH:19]=[C:20]([NH:23][C:24]([C:26]3[S:27][CH:28]=[CH:29][CH:30]=3)=[NH:25])[CH:21]=[CH:22][C:14]1=2)[CH2:3][C:4]([OH:6])=[O:5]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 178484230HCID 178484230, compound

Product 1

HCID 178484231HCID 178484231, compoundYield 96%

Conditions

Temperature
0 °C

Procedure

An oven dried round bottom flask, equipped with a magnetic stirbar under argon, was charged with tert-butyl 2-(methyl(2-(7-(thiophene-2-carboximidamido)-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethyl)amino)acetate (200 mg, 0.448 mmol) in CH2Cl2 (3 mL), and the solution was cooled to 0° C. (ice/water bath). To this solution was added anisole (0.098 mL, 0.896 mmol) followed by the dropwise addition of trifluoroacetic acid (2.92 mL, 26.9 mmol). The reaction was stirred at 0° C. for 20 minutes. The ice bath was then removed, and the mixture was stirred for 3 additional hours. At this time, the mixture was concentrated and treated with 4.0 M HCl in 1,4-dioxane (4 mL). The resulting suspension was diluted with Et2O (20 mL) and then stirred for 20 minutes. The mixture was filtered, and the solid was washed with Et2O (20 mL). The solid was dried under reduced pressure to give compound 17 as light yellow powder (200 mg, 96%). An HPLC analysis indicated that the sample contained ˜3.4% of the starting material. 1H-NMR (CD3OD) δ 7.99 (d, J=5.1 Hz, 1H), 7.97 (d, J=3.6 Hz, 1H), 7.31 (pseudo t, J=4.5 Hz, 1H), 7.11-6.99 (m, 2H), 6.95 (d, J=8.7 Hz, 1H), 4.16 (s, 2H), 3.81 (brt, J=6.9 Hz, 2H), 3.68 (brt, J=4.8 Hz, 2H), 3.52-3.39 (m, 2H), 3.10 (brt, J=4.8 Hz, 2H), 3.03 (s, 3H); ESI-MS (positive ion mode): 391 (MH+, free base, 100); ESI-MS (negative ion mode): 389 (M-1, free base, 100); ESI-HRMS calculated for C18H23N4O2S2 (MH+, free base): 391.1256, Observed: 391.1255; HPLC purity: 96.64% a/a.

Workup

  1. customAn oven dried round bottom flask
  2. customequipped with a magnetic stirbar under argon
  3. customThe ice bath was then removed
  4. stirringthe mixture was stirred for 3 additional hours
  5. concentrationAt this time, the mixture was concentrated
  6. additiontreated with 4.0 M HCl in 1,4-dioxane (4 mL)
  7. additionThe resulting suspension was diluted with Et2O (20 mL)
  8. stirringstirred for 20 minutes
  9. filtrationThe mixture was filtered
  10. washthe solid was washed with Et2O (20 mL)
  11. customThe solid was dried under reduced pressure

Sources & evidence

ORD record
ord-96c533aa66664a82837dc916caaca9f3
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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