Ammonium Chloride → 6-amino-1-tert-butyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide

HRID 45798Notes

Reaction equation

HRID 45798 reaction equation
[C:1]([N:5]1[C:17]2[C:16]3[N:15]=[C:14]([S:18][CH3:19])[N:13]=[CH:12][C:11]=3[CH:10]=[CH:9][C:8]=2[C:7]([C:20]([O:22]CC)=O)=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[Cl-].[NH4+:26].[Li][N:28]([Si](C)(C)C)[Si](C)(C)C>C1COCC1>[C:1]([N:5]1[C:17]2[C:16]3[N:15]=[C:14]([S:18][CH3:19])[N:13]=[CH:12][C:11]=3[CH:10]=[CH:9][C:8]=2[C:7]([C:20]([NH2:28])=[O:22])=[N:6]1)([CH3:2])([CH3:4])[CH3:3].[NH2:26][C:12]1[C:11]2[CH:10]=[CH:9][C:8]3[C:7]([C:20]([NH2:28])=[O:22])=[N:6][N:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[C:17]=3[C:16]=2[N:15]=[C:14]([S:18][CH3:19])[N:13]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 68067407Ethyl 1-tert-butyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxylateHCID 178418261HCID 178418261, compound

Product 2

HCID 573890561-tert-butyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamideHCID 573890576-amino-1-tert-butyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamideYield 6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Ethyl 1-tert-butyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate (170 mg 0.494 mmol) was suspended in 4 ml of anhydrous THF and ammonium chloride (80 mg 1.48 mmol) was added. The reaction mixture was cooled to 0° C. and LiN(TMS)2 1M in THF (3 ml, 3 mmol) was added; the reaction was stirred for 2 hours. The solvent was then evaporated to dryness, the residue suspended in water and filtered. The crude was purified via silica gel column chromatography eluting with DCM/MeOH 97/3 to give 1-tert-butyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide, 100 mg (65% yield), and 6-amino-1-tert-butyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide 10 mg (6%). LC/MS (254 nm) HPLC method 2 Rt 6.07 min. 1H NMR (401 MHz, DMSO-d6) δ 9.49 (s, 1H), 8.42 (d, J=8.54 Hz, 1H), 7.80 (d, J=8.79 Hz, 1H), 7.75 (br. s., 1H), 7.53 (br. s., 1H), 2.74 (s, 3H), 2.00 (s, 9H). HRMS (ESI) calcd for C15H17N5OS [M+H]+ 316.1227 found 316.1224.

Workup

  1. customThe solvent was then evaporated to dryness
  2. filtrationfiltered
  3. customThe crude was purified via silica gel column chromatography
  4. washeluting with DCM/MeOH 97/3

Sources & evidence

ORD record
ord-8b7fb34f16d5447495eb238cd73762c2
Source dataset
uspto-grants-2013_09
Patent number
US08541576B2

Reaction notes

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