Dimethylformamide → HCID 44158490, compound

HRID 1926358Notes

Reaction equation

HRID 1926358 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:27])=[N:12][CH:13]=[C:14]([C:16]2[CH:17]=[N:18][N:19]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[CH:20]=2)[CH:15]=1.C([O-])([O-])=O.[Cs+].[Cs+].CN(C=O)C.Cl[CH2:40][C:41]([O:43]C)=[O:42]>>[NH2:27][C:11]1[N:12]=[CH:13][C:14]([C:16]2[CH:17]=[N:18][N:19]([CH:21]3[CH2:22][CH2:23][N:24]([CH2:40][C:41]([OH:43])=[O:42])[CH2:25][CH2:26]3)[CH:20]=2)=[CH:15][C:10]=1[C:2]1[S:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 7295Methyl chloroacetateHCID 10796Cesium carbonateHCID 44160138HCID 44160138, compound

Product 1

HCID 44158490HCID 44158490, compound

Conditions

Temperature
40 °C

Procedure

A mixture of 3-benzothiazol-2-yl-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine (211.0 mg, 0.5604 mmol), Cs2CO3 (730 mg, 2.24 mmol), and DMF (10 mL, 0.1 mol) at 0° C. was charged with methyl chloroacetate (0.0493 mL, 0.560 mmol) and then heated at 40° C. overnight. The solvent was removed in vacuo, and the material was dry-loaded onto silica gel for column chromatography, eluting with 2→5% MeOH/DCM. The fractions containing the pure ester were concentrated in vacuo and redissolved in conc. HCl. The material was transferred to a sealed tube, and heated overnight at 50° C. The HCl was removed using the corrosive pump to afford the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ=2.36 (br. s., 4H), 3.34 (d, J=11.4 Hz, 2H), 3.71 (d, J=9.1 Hz, 2H), 4.19 (br. s., 2H), 4.31-4.41 (m, 1H), 4.51 (br. s., 2H), 7.54-7.60 (m, 1H), 7.61-7.67 (m, 1H), 8.12-8.20 (m, 2H), 8.24 (d, J=7.1 Hz, 1H), 8.52 (d, J=1.3 Hz, 1H), 8.58-8.65 (m, 2H), 10.49 (br, s., 1H). MS (ES+): m/z=435.09 (100) [MH+]. HPLC: tR=2.24 min (ZQ2, polar—5 min).

Workup

  1. customThe solvent was removed in vacuo
  2. washeluting with 2→5% MeOH/DCM
  3. additionThe fractions containing the pure ester
  4. concentrationwere concentrated in vacuo
  5. dissolutionredissolved in conc. HCl
  6. customThe material was transferred to a sealed tube
  7. temperatureheated overnight at 50° C
  8. customThe HCl was removed

Sources & evidence

ORD record
ord-af12f2c955a54bd28d1a92bbfd62566a
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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