Bromine → 1-(2-Amino-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl)-ethanone

HRID 1795928Notes

Reaction equation

HRID 1795928 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][C:7](=O)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].BrBr.[NH2:13][C:14]([NH2:16])=[S:15]>C(O)(=O)C>[C:1]([N:4]1[CH2:9][CH2:8][C:7]2[N:13]=[C:14]([NH2:16])[S:15][C:6]=2[CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 24408BromineHCID 122563N-Acetyl-4-piperidoneHCID 2723790Thiourea

Product 1

HCID 150176501-(2-Amino-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl)-ethanoneYield 10.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

N-Acetyl4-piperidone (7.05 g, 0.05 mol) in acetic acid (35 mL) was treated dropwise with bromine (8.0 g, 0.05 mol) in acetic acid (10 mL) at room temperature. After 4 h, the formed precipitate was collected on a filter, washed with diethyl ether and air-dried. This crude intermediate (3.01 g) was dissolved in ethanol (20 mL) and after the addition of thiourea (0.76 g, 10.0 mmol)the reaction mixture was refixed for 4 h. The solvent was removed in vacuo. Water (20 mL) was added and the pH was adjusted to 9. Extraction with DCM, drying (sodium sulfate) and removal of the organic phase gave 1.1 g of a crude product. Modification by flash chromatography on silica gel gave 202 mg (10%) of 5-acetyl4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-ylamine. This compound was sulfonylated with 3-chloro-2-methylbenzene sulfonyl chloride (234 mg, 1.02 mmol) in pyridine according to METHOD A. After workup, the final product was crystallised from methanol to afford 75 mg (%) of white crystals: 1H NMR (DMSO-d6, 70° C.) δ 2.05 (s, 3H), 2.66 (s, 3H), 3.09 (m, 2H), 3.69 (m, 2H), 4.38 (m 2H), 7.37 (t, 1H), 7.64 (d, 1H), 7.91 (d, 1H), 12.53 (br s, NH).

Workup

  1. customthe formed precipitate was collected on a filter
  2. washwashed with diethyl ether
  3. customair-dried
  4. dissolutionThis crude intermediate (3.01 g) was dissolved in ethanol (20 mL)
  5. waitwas refixed for 4 h
  6. customThe solvent was removed in vacuo
  7. additionWater (20 mL) was added
  8. extractionExtraction with DCM
  9. customdrying
  10. custom(sodium sulfate) and removal of the organic phase
  11. customgave 1.1 g of a crude product

Sources & evidence

ORD record
ord-c1f69bf9952c44a08d8e161415b0845e
Source dataset
uspto-grants-2006_04
Patent number
US07030135B2

Reaction notes

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