Lithium Hexamethyldisilazide → 6-chloro-N-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-5-methyl-2-[3-(quinolin-2-yl)propoxy]pyrimidin-4-amine

HRID 1626368노트

반응식

HRID 1626368 반응식
[Cl:1][C:2]1[N:7]=[C:6](S(C)(=O)=O)[N:5]=[C:4]([NH:12][CH2:13][C:14]2[S:18][C:17]([CH3:19])=[N:16][C:15]=2[CH3:20])[C:3]=1[CH3:21].[N:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][C:23]=1[CH2:32][CH2:33][CH2:34][OH:35].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([O:35][CH2:34][CH2:33][CH2:32][C:23]2[CH:24]=[CH:25][C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:22]=2)[N:5]=[C:4]([NH:12][CH2:13][C:14]2[S:18][C:17]([CH3:19])=[N:16][C:15]=2[CH3:20])[C:3]=1[CH3:21]

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 218061343-(Quinolin-2-yl)propan-1-olHCID 866881616-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methyl-2-methylsulfonyl-pyrimidin-4-amine

생성물 1

HCID 569494516-chloro-N-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-5-methyl-2-[3-(quinolin-2-yl)propoxy]pyrimidin-4-amine

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of 6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methyl-2-methylsulfonyl-pyrimidin-4-amine F5 (51 mg, 0.15 mmol) and 3-(quinolin-2-yl)propan-1-ol G6 (25 mg, 0.13 mmol) in 3 mL of THF was added LiHMDS (200 μL of a 1M solution in THF, 0.20 mmol). After stirring for 2 hours, the reaction was quenched by the addition of a saturated ammonium chloride solution. The mixture was partitioned between a saturated solution of NaHCO3 and EtOAc, the layers were separated, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated by rotary evaporation. The residue was purified by silica gel flash column chromatography (EtOAc/hexanes gradient) to provide 17 mg (28%) of G7 as an off-white solid. 1H NMR δ (400 MHz, CDCl3): 8.1-8.0 (2H, m), 7.75 (1H, m), 7.65 (1H, m), 7.5 (1H, m), 7.35 (1H, m), 4.9 (1H, m), 4.7 (2H, d), 4.4 (2H, t), 3.15 (2H, t), 2.6 (3H, s), 2.35 (5H, m), 2.0 (3H, s). HRMS (ES) calculated M+H for C23H24ClN5OS: 454.1463. Found. 454.1455.

후처리

  1. customthe reaction was quenched by the addition of a saturated ammonium chloride solution
  2. customThe mixture was partitioned between a saturated solution of NaHCO3 and EtOAc
  3. customthe layers were separated
  4. extractionthe aqueous layer was extracted twice with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated by rotary evaporation
  8. customThe residue was purified by silica gel flash column chromatography (EtOAc/hexanes gradient)
  9. customto provide 17 mg (28%) of G7 as an off-white solid

출처 및 근거

ORD 기록
ord-896c2e93c73947f095dc833fd99be430
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785467B2

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