Sodium Bicarbonate → N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-N-cyclopropyl-3-(methylthio)propanamide

HRID 515136Notes

Reaction equation

HRID 515136 reaction equation
Cl.[Cl:2][C:3]1[N:4]=[C:5]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[S:6][C:7]=1[NH:8][CH:9]1[CH2:11][CH2:10]1.[CH3:18][S:19][CH2:20][CH2:21][C:22](Cl)=[O:23].C([O-])(O)=O.[Na+]>CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[Cl:2][C:3]1[N:4]=[C:5]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[S:6][C:7]=1[N:8]([CH:9]1[CH2:11][CH2:10]1)[C:22](=[O:23])[CH2:21][CH2:20][S:19][CH3:18]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 129214403-(Methylthio)propionyl ChlorideHCID 86704357HCID 86704357, compound

Product 1

HCID 86704356N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-N-cyclopropyl-3-(methylthio)propanamideYield 23.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-chloro-N-cyclopropyl-2-(pyridin-3-yl)thiazol-5-amine HCl salt (288 mg, 1 mmol) and DMAP (305 mg, 2.500 mmol) in CH2ClCH2Cl (1 mL) was added 3-(methylthio)propanoyl chloride (166 mg, 1.200 mmol), and the mixture stirred at room temperature for 1 h. The mixture was diluted with ethyl acetate, mixed with aqueous NaHCO3 (10 mL). The organic phase was separated, rinsed with brine (2×), dried over MgSO4 and concentrated in vacuo to give a yellow gum. This gum was purified on reverse phase column chromatography (C-18, CH3CN/H2O) to give N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-N-cyclopropyl-3-(methylthio)propanamide (82 mg, 22%) as a brown gum: 1H NMR (400 MHz, CDCl3) δ 9.10 (s, 0.6H), 9.02 (s, 0.4H), 8.71 (s, 6H), 8.61 (d, J=3.4 Hz, 0.4H), 8.21 (d, J=7.6 Hz, 1H), 8.19-8.10 (m, 1H), 7.41 (d, J=5.6, 0.6H), 7.35 (dd, J=8.3, 4.5 Hz, 0.4H), 3.16 (bs, 1H), 2.91 (s, 3H), 2.88-2.72 (m, 2H), 2.11 (m, 2H), 0.85 (m, 4H); ESIMS (m/z) 354.56 ([M+H]+).

Workup

  1. customThe organic phase was separated
  2. washrinsed with brine (2×)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customto give a yellow gum
  6. customThis gum was purified on reverse phase column chromatography (C-18, CH3CN/H2O)

Sources & evidence

ORD record
ord-d8d59d8f471a4875940c23c49c4d9bf4
Source dataset
uspto-grants-2015_08
Patent number
US09108952B2

Reaction notes

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