4-Aminopyrimidine → 4-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)quinazoline-7-sulfonamide

HRID 1473689Notes

Reaction equation

HRID 1473689 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[N:11]=[CH:10][N:9]=2)=[C:4]([O:33][CH3:34])[CH:3]=1.[N:35]1[CH:40]=[CH:39][C:38]([NH2:41])=[N:37][CH:36]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:41][C:38]4[CH:39]=[CH:40][N:35]=[CH:36][N:37]=4)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[N:11]=[CH:10][N:9]=2)=[C:4]([O:33][CH3:34])[CH:3]=1

Participants

5

Reactant 3

HCID 689584-AminopyrimidineHCID 2733832Lithium HexamethyldisilazideHCID 86687771Perfluorophenyl 4-(4-chloro-2-methoxyphenyl)quinazoline-7-sulfonate

Product 1

HCID 866877734-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)quinazoline-7-sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A flask was charged with perfluorophenyl 4-(4-chloro-2-methoxyphenyl)quinazoline-7-sulfonate (Intermediate AAAAAA; 1.0 g, 1.935 mmol), pyrimidin-4-amine (0.193 g, 2.032 mmol), and THF (19.35 ml) and cooled to 0° C. LHMDS (1.0M in THF) (4.06 ml, 4.06 mmol) was added drop wise and the reaction was stirred for 30 minutes. The reaction was quenched with saturated ammonium chloride solution, 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 80 g, gradient elution 0-10% MeOH:DCM) to afford 4-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)quinazoline-7-sulfonamide as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ=13.28 (br. s., 1H), 9.46 (s, 1H), 8.57 (t, J=1.0 Hz, 1H), 8.48 (d, J=1.7 Hz, 1H), 8.22 (d, J=6.5 Hz, 1H), 8.03 (dd, J=1.9, 8.8 Hz, 1H), 7.83 (d, J=8.7 Hz, 3H), 7.47 (d, J=8.1 Hz, 1H), 7.38 (d, J=1.9 Hz, 1H), 7.25 (dd, J=2.0, 8.1 Hz, 1H), 7.00 (d, J=6.7 Hz, 1H), 3.72 (s, 3H). m/z (ESI) 428.2 (M+H)+.

Workup

  1. customThe reaction was quenched with saturated ammonium chloride solution
  2. additiondiluted with ethyl acetate
  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 80 g, gradient elution 0-10% MeOH:DCM)

Sources & evidence

ORD record
ord-1468560657884b62ba7b93518254f1d3
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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