Thiosemicarbazide → HCID 136068476, compound

HRID 2189242Notes

Reaction equation

HRID 2189242 reaction equation
[CH:1]([C:3]1[CH:4]=[CH:5][C:6]([O:32]C)=[C:7]([C:9]2[N:18]=[C:17]([NH:19][C@H:20]3[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21]3)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)[CH:8]=1)=O.[NH2:34][NH:35][C:36]([NH2:38])=[S:37]>C(O)C>[NH2:38][C:36]1[S:37][C:1]([C:3]2[CH:4]=[CH:5][C:6]([OH:32])=[C:7]([C:9]3[N:18]=[C:17]([NH:19][C@H:20]4[CH2:24][CH2:23][NH:22][CH2:21]4)[C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[N:10]=3)[CH:8]=2)=[N:34][N:35]=1

Participants

4

Reactant 2

HCID 2723789ThiosemicarbazideHCID 86761715HCID 86761715, compound

Product 1

HCID 136068476HCID 136068476, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(S)-tert-Butyl 3-(2-(5-formyl-2-methoxyphenyl)quinazolin-4-ylamino)pyrrolidine-1-carboxylate (0.160 g, 0.357 mmol) was dissolved in ethanol (2 mL) and thiosemicarbazide (0.033 g, 0.362 mmol) was added and the solution was stirred at room temperature for 16 h. The solid was filtered off and washed with ethanol (2×1 mL). The solid was suspended in water (16 mL) and ferric chloride (0.267 g, 1.00 mmol) was added and the solution was heated at 60° C. for 16 h. A further portion of ferric chloride (0.267 g, 1.00 mmol) was added and the solution heated at 90° C. for 2.5 h. The reaction mixture was partitioned between water (20 mL) and dichloromethane (20 mL), but the bright yellow product was visibly in the aqueous phase so the aqueous phase was concentrated in vacuo and the residue was purified by ion exchange chromatography on SCX-2 (solute acidic resin (2 g), eluting with methanol and then 1 M ammonia in methanol. The basic fractions were combined and purified by HPLC. Semi-prep HPLC was performed on an Agilent 1200 series with a Phenomex Gemini 250 mm×10 mm i.d. column at a temperature of 20 C and a flow rate of 5 mL/min using a gradient of 10%-100% acetonitrile in water over 30 mins.

Workup

  1. filtrationThe solid was filtered off
  2. washwashed with ethanol (2×1 mL)
  3. temperaturethe solution was heated at 60° C. for 16 h
  4. temperaturethe solution heated at 90° C. for 2.5 h
  5. customThe reaction mixture was partitioned between water (20 mL) and dichloromethane (20 mL)
  6. concentrationwas concentrated in vacuo
  7. customthe residue was purified by ion exchange chromatography on SCX-2 (solute acidic resin (2 g)
  8. washeluting with methanol
  9. custompurified by HPLC
  10. customover 30 mins

Sources & evidence

ORD record
ord-658ae5c3da2b4ddd84fa3f33681d7e4f
Source dataset
uspto-grants-2012_12
Patent number
US08324226B2

Reaction notes

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