Dichloromethane → HCID 86626540, compound

HRID 1851752Notes

Reaction equation

HRID 1851752 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](O)=[O:4].[CH3:8][N:9]1[CH2:14][CH2:13][N:12]([C:15]2[N:20]=[CH:19][C:18]([C:21]3[S:22][C:23]4[CH:29]=[C:28]([NH2:30])[CH:27]=[CH:26][C:24]=4[N:25]=3)=[CH:17][CH:16]=2)[CH2:11][CH2:10]1.C(N(C(C)C)CC)(C)C.C(Cl)Cl>C(Cl)Cl.C1COCC1>[F:1][C:2]([F:7])([F:6])[C:3]([NH:30][C:28]1[CH:27]=[CH:26][C:24]2[N:25]=[C:21]([C:18]3[CH:19]=[N:20][C:15]([N:12]4[CH2:11][CH2:10][N:9]([CH3:8])[CH2:14][CH2:13]4)=[CH:16][CH:17]=3)[S:22][C:23]=2[CH:29]=1)=[O:4]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 67276449HCID 67276449, compound

Product 1

HCID 86626540HCID 86626540, compoundYield 37.8%

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

A mixture of 2-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1,3-benzothiazol-6-amine trifluoroacetate (0.12 g, 0.27 mmol), ethyl chloroformiate (36 μL, 0.38 mmol) and diisopropylethylamine (0.238 mL, 1.44 mmol) in DCM/THF (1:1, 7 mL) was stirred at r.t. overnight. Additional DCM was added before washing the sol. with sat. sodium hydrogencarbonate and then brine. The sol. was then dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by prep. HPLC, to give intermediate 2,2,2-trifluoro-N-{2-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1,3-benzothiazol-6-yl}acetamide (43 mg). MS m/z (M+H) 422, (M−H) 420. To this intermediate (43 mg) in THF (5 mL) was added lithium aluminium hydride (12 mg, 0.3 mmol). The r.m. was refluxed for 1.5 h then allowed to come to r.t. Two drops of sat. Na2SO4, followed by ethyl acetate was added and the mixture was stirred for a few minutes. The organic layer was washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by prep. HPLC to yield the title compound (25 mg) as a pale yellow solid. 1H NMR (MeOH-D4) δ 8.59 (d, 1H) 7.97 (dd, 1 H) 7.60 (d, 1 H) 7.11 (d, 1 H) 6.75-6.87 (m, 2 H) 3.80 (q, 2 H) 3.55-3.70 (m, 4 H) 2.50-2.61 (m, 4 H) 2.33 (s, 3 H); MS m/z (M+H) 408, (M−H) 406.

Workup

  1. washbefore washing the sol. with sat. sodium hydrogencarbonate
  2. dry with materialThe sol. was then dried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe residue was purified by prep

Sources & evidence

ORD record
ord-a6026b31afcf42e2aeade0d9a3cb86be
Source dataset
uspto-grants-2015_02
Patent number
US08957215B2

Reaction notes

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