Potassium Carbonate → HCID 44125204, compound

HRID 2040998Notes

Reaction equation

HRID 2040998 reaction equation
[N:1]1([C@@H:7]2[CH2:11][CH2:10][N:9]([C:12]3[S:13][C:14]4[CH:20]=[C:19]([OH:21])[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:23]1[CH:32]=[CH:31][C:26]([C:27]([NH:29][CH3:30])=[O:28])=[CH:25][N:24]=1.C([O-])([O-])=O.[K+].[K+]>CN(C)C=O.C(Cl)Cl>[CH3:30][NH:29][C:27](=[O:28])[C:26]1[CH:31]=[CH:32][C:23]([O:21][C:19]2[CH:18]=[CH:17][C:15]3[N:16]=[C:12]([N:9]4[CH2:10][CH2:11][C@@H:7]([N:1]5[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]5)[CH2:8]4)[S:13][C:14]=3[CH:20]=2)=[N:24][CH:25]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 123642306-Chloro-N-methylnicotinamideHCID 44124594HCID 44124594, compound

Product 1

HCID 44125204HCID 44125204, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-ol (Example 47, 20 mg, 0.066 mmol), 6-chloro-N-methylnicotinamide (Example 71A, 11 mg, 0.066 mmol) and K2CO3 (27 mg, 0.20 mmol) in N,N-dimethylformamide (0.25 mL) was heated to 100° C. for 1 hour, cooled, diluted with CH2Cl2, filtered, and concentrated. The residue was purified by HPLC as described in Example 66. The product was further purified by chromatography on silica gel eluting with a gradient of 2 to 10% (9:1 methanol:ammonium hydroxide) in CH2Cl2 to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.44-1.53 (m, 2H), 1.59-1.67 (m, 4H), 1.94-2.10 (m, 1H), 2.24-2.34 (m, 1H), 2.39-2.57 (m, 4H), 2.95-3.06 (m, 1H), 3.01 (d, J=4.7 Hz, 3H), 3.43 (t, J=9.3 Hz, 1H), 3.48-3.60 (m, 1H), 3.70-3.89 (m, 2H), 6.09-6.18 (m, 1H), 6.92 (dd, J=8.5, 0.7 Hz, 1H), 7.07 (dd, J=8.5, 2.4 Hz, 1H), 7.40 (d, J=2.4 Hz, 1H), 7.58 (d, J=8.8 Hz, 1H), 8.12 (dd, J=8.6, 2.5 Hz, 1H), 8.53 (dd, J=2.7, 0.7 Hz, 1H); MS (DCI/NH3) m/z 438 (M+H)+.

Workup

  1. temperaturecooled
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customThe residue was purified by HPLC
  5. customThe product was further purified by chromatography on silica gel eluting with a gradient of 2 to 10% (9:1 methanol:ammonium hydroxide) in CH2Cl2

Sources & evidence

ORD record
ord-58307e165fa14ef5bb0c00dcb7837f6d
Source dataset
uspto-grants-2013_11
Patent number
US08580968B2

Reaction notes

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