Methanol → HCID 67276608, compound

HRID 1698070Notes

Reaction equation

HRID 1698070 reaction equation
[N+:1]([C:4]1[CH:31]=[CH:30][C:7]2[N:8]=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([N:17]4[CH2:22][CH2:21][N:20]([C:23](OC(C)(C)C)=O)[CH2:19][CH2:18]4)=[N:15][CH:16]=3)[S:10][C:6]=2[CH:5]=1)([O-:3])=[O:2].[C:32]([OH:38])([C:34]([F:37])([F:36])[F:35])=[O:33].CO>C(Cl)Cl>[F:35][C:34]([F:37])([F:36])[C:32]([OH:38])=[O:33].[CH3:23][N:20]1[CH2:19][CH2:18][N:17]([C:14]2[N:15]=[CH:16][C:11]([C:9]3[S:10][C:6]4[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:31]=[CH:30][C:7]=4[N:8]=3)=[CH:12][CH:13]=2)[CH2:22][CH2:21]1

Participants

5

Reactant 3

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 57553414HCID 57553414, compound

Product 1

HCID 67276608HCID 67276608, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

To tert-butyl 4-[5-(6-nitro-1,3-benzothiazol-2-yl)pyridin-2-yl]piperazine-1-carboxylate (0.29 g) in DCM (15 mL) was added TFA (1.5 mL) before stirring o.n. at r.t. The solvent was thereafter removed by blowing with nitrogen and the residue, crude 6-nitro-2-(6-piperazin-1-ylpyridin-3-yl)-1,3-benzothiazole (MS m/z [M+H] 342.), was used directly in the next step. To this residue in methanol (3 mL), was added formaldehyde (37% aq., 0.25 mL) and sodium cyanoborohydride (74 mg), followed by heating at 70° C. for 5 minutes. A thick solid formed and additional methanol (3 mL) was added. The mixture was stirred at r.t. for 1 h, then filtered. The solid was washed with ice-cold methanol and was then dried under vacuum over P2O5, to give intermediate 2-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-6-nitro-1,3-benzothiazole trifluoroacetate (0.26 g) as a solid. MS m/z (M+H) 356. This intermediate (0.26 g) was dissolved in methanol (8 mL) and ammonia (7M in methanol, 2 mL) was added. The flask was evacuated and flushed with argon. Palladium (10% on carbon, 30 mg) was added and the flask was evacuated and filled with hydrogen gas. The reaction mixture was shaken under an atmosphere of hydrogen o.n. at r.t. The mixture was thereafter filtered through diatomaceous earth and evaporated in vacuo, to give the title compound (0.22 g) as a white solid. 1H NMR (CHLOROFORM-d) δ 8.67 (d, 1H) 8.05 (dd, 1H) 7.70 (d, 1H) 7.04 (d, 1H) 6.74 (dd, 1H) 6.63 (d, 1H) 3.33-4.01 (m, 6H) 2.42-2.55 (m, 4H) 2.30 (s, 3H); MS m/z (M+H) 326.

Workup

  1. customat r.t
  2. customThe solvent was thereafter removed
  3. additionTo this residue in methanol (3 mL), was added formaldehyde (37% aq., 0.25 mL) and sodium cyanoborohydride (74 mg)
  4. customA thick solid formed
  5. stirringThe mixture was stirred at r.t. for 1 h
  6. filtrationfiltered
  7. washThe solid was washed with ice-cold methanol
  8. dry with materialwas then dried under vacuum over P2O5

Sources & evidence

ORD record
ord-45245dd6207e4b9a906f65f67ce28999
Source dataset
uspto-grants-2012_04
Patent number
US08163928B2

Reaction notes

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