Trifluoroacetic acid → 4-(2-(pyridin-4-yl)pyrrolidin-1-yl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide

HRID 1473694Notes

Reaction equation

HRID 1473694 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([C:21]1[S:25][N:24]=[CH:23][N:22]=1)[S:7]([C:10]1[CH:19]=[C:18]2[C:13]([C:14](=O)[NH:15][CH:16]=[N:17]2)=[CH:12][CH:11]=1)(=[O:9])=[O:8].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C1CCN2C(=NCCC2)CC1.[NH:70]1[CH2:74][CH2:73][CH2:72][CH:71]1[C:75]1[CH:80]=[CH:79][N:78]=[CH:77][CH:76]=1.C(O)(C(F)(F)F)=O>C(#N)C.C(OCC)(=O)C>[N:78]1[CH:79]=[CH:80][C:75]([CH:71]2[CH2:72][CH2:73][CH2:74][N:70]2[C:14]2[C:13]3[C:18](=[CH:19][C:10]([S:7]([NH:6][C:21]4[S:25][N:24]=[CH:23][N:22]=4)(=[O:9])=[O:8])=[CH:11][CH:12]=3)[N:17]=[CH:16][N:15]=2)=[CH:76][CH:77]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27716644-(Pyrrolidin-2-yl)pyridine2×HCID 136409075N-(2,4-dimethoxybenzyl)-4-oxo-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroquinazoline-7-sulfonamide

Product 1

HCID 866877784-(2-(pyridin-4-yl)pyrrolidin-1-yl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of N-(2,4-dimethoxybenzyl)-4-oxo-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroquinazoline-7-sulfonamide (0.611 g, 1.330 mmol) and BOP (0.765 g, 1.729 mmol) in acetonitrile (6.65 ml) was added DBU (0.301 ml, 1.995 mmol). The reaction was stirred for 10 minutes at 40° C. 4-(pyrrolidin-2-yl)pyridine (0.272 ml, 1.995 mmol) was added and the reaction was stirred for 8 hours at 40° C. 4-(pyrrolidin-2-yl)pyridine (0.272 ml, 1.995 mmol) was added and the reaction was stirred for four hours at 40° C. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 40 g, gradient elution 0-10% MeOH:DCM). The material was dissolved in DCM and TFA (0.2 ml, 2.60 mmol) was added. The reaction was stirred for one hour at room temperature. The reaction was concentrated and purified via column chromatography (RediSep Gold 12 g, gradient elution 0-10% MeOH:DCM) to afford 4-(2-(pyridin-4-yl)pyrrolidin-1-yl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide as a light yellow solid. (ESI) 440.2 (M+H)+.

Workup

  1. stirringthe reaction was stirred for 8 hours at 40° C
  2. stirringthe reaction was stirred for four hours at 40° C
  3. washwashed with water
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organic layers were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified via column chromatography (RediSep Gold 40 g, gradient elution 0-10% MeOH:DCM)
  9. dissolutionThe material was dissolved in DCM
  10. stirringThe reaction was stirred for one hour at room temperature
  11. concentrationThe reaction was concentrated
  12. custompurified via column chromatography (RediSep Gold 12 g, gradient elution 0-10% MeOH:DCM)

Sources & evidence

ORD record
ord-f2e1fbdc4d634603afaef0a9bf9989ca
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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