Chloride → (R)-ethyl 2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole-6-carboxylate

HRID 1692011Notes

Reaction equation

HRID 1692011 reaction equation
Cl[C:2]1[S:3][C:4]2[CH:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:8]=[CH:7][C:5]=2[N:6]=1.Cl.Cl.[NH:18]1[CH2:22][CH2:21][C@@H:20]([N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[CH2:19]1.C(N(CC)CC)C.[Cl-].C1C=C2C(C(O)(O)C(=O)C2=CC=1)=O>CN(C)C=O.O.C(OCC)(=O)C>[N:23]1([C@@H:20]2[CH2:21][CH2:22][N:18]([C:2]3[S:3][C:4]4[CH:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:8]=[CH:7][C:5]=4[N:6]=3)[CH2:19]2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

9

Reactant 5

HCID 312ChlorideHCID 8471TriethylamineHCID 10236NinhydrinHCID 12692400Ethyl 2-chloro-1,3-benzothiazole-6-carboxylateHCID 669057171-[(3R)-pyrrolidin-3-yl]piperidine dihydrochloride

Product 1

HCID 44124706(R)-ethyl 2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole-6-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of ethyl 2-chlorobenzo[d]thiazole-6-carboxylate (1.62 g, 6.72 mmol), (R)-1-(pyrrolidin-3-yl)piperidine dihydrochloride (Reference Example 5c, 1.80 g, 7.94 mmol), and triethylamine (5.11 mL, 36.66 mmol) in N,N-dimethylformamide (19 mL) was stirred at ambient temperature for 17 hours. According to TLC (100% ethyl acetate) the spot for starting chloride was replaced by a much lower Rf, ninhydrin-positive spot. The reaction mixture was diluted with water (400 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were washed with brine (2×200 mL) then dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on an Analogix IF-280 (Analogix SF40-120 g, 99:1 ethyl acetate/methanol). Fractions containing product were combined and concentrated under reduced pressure to provide the title compound. 1H NMR (300 MHz, CD3OD) δ ppm 8.34 (d, J=1.7 Hz, 1H), 7.96 (dd, J=1.7 Hz, 8.5, 1H), 7.49 (d, J=8.6 Hz, 1H), 4.36 (q, J=7.1 Hz, 2H), 3.82 (dt, J=8.8, 18.3 Hz, 2H), 3.63-3.50 (m, 1H), 3.41 (t, J=9.3 Hz, 1H), 3.16-3.02 (m, 1H), 2.67-2.43 (m, 4H), 2.43-2.30 (m, 1H), 2.11-1.93 (m, 1H), 1.72-1.59 (m, 4H), 1.58-1.45 (m, 2H), 1.39 (t, J=7.1 Hz, 3H); MS (DCI/NH3) m/z 360 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (3×75 mL)
  2. washThe combined organic extracts were washed with brine (2×200 mL)
  3. dry with materialthen dried (MgSO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by column chromatography on an Analogix IF-280 (Analogix SF40-120 g, 99:1 ethyl acetate/methanol)
  7. additionFractions containing product
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-090f7bab2f0a476a8d2807043df06efa
Source dataset
uspto-grants-2012_04
Patent number
US08153813B2

Reaction notes

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