Lithium diisopropylamide → HCID 70977464, compound

HRID 2402399Notes

Reaction equation

HRID 2402399 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[S:12][CH:11]=[N:10][CH:9]=2)[N:5]=[C:4]([NH:13][C:14]2[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[CH:3]=1.[Li+].CC([N-]C(C)C)C.[Br:32][C:33]1[C:42]2[CH2:41][CH2:40][CH2:39][C:38](=[O:43])[C:37]=2[CH:36]=[CH:35][C:34]=1[C:44]([O:46][CH3:47])=[O:45]>C1COCC1>[Br:32][C:33]1[C:42]2[CH2:41][CH2:40][CH2:39][C:38]([OH:43])([C:11]3[S:12][C:8]([C:6]4[CH:7]=[C:2]([CH3:1])[CH:3]=[C:4]([NH:13][C:14]5[CH:19]=[C:18]([C:20]([F:23])([F:21])[F:22])[CH:17]=[CH:16][N:15]=5)[N:5]=4)=[CH:9][N:10]=3)[C:37]=2[CH:36]=[CH:35][C:34]=1[C:44]([O:46][CH3:47])=[O:45]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 709773814-methyl-6-(1,3-thiazol-5-yl)-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amineHCID 70977535Methyl 1-bromo-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate

Product 1

HCID 70977464HCID 70977464, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To an oven-dried flask was added 4-methyl-6-(thiazol-5-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)pyridin-2-amine (300 mg, 0.892 mmol) and THF (7.1 mL) and the solution was cooled to −78° C. LDA (1.34 mL, 2.68 mmol) was slowly added, and the resulting mixture was stirred for 30 minutes at −78° C. In a separate oven-dried flask, methyl 1-bromo-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate (316 mg, 1.12 mmol) was then dissolved in THF (5 mL), and this solution was added to the reaction mixture, which was then allowed to warm to rt. over a period of 3 hours. The reaction was then quenched with MeOH (5 mL) and concentrated. Purification by chromatography on silica gel furnished methyl 1-bromo-5-hydroxy-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate 17A (210 mg, 38%) as a light yellow solid. MS ESI calcd for C27H22BrF3N4O3S [M+H]+ 619, found 619.

Workup

  1. customIn a separate oven-dried flask
  2. additionthis solution was added to the reaction mixture, which
  3. temperatureto warm to rt
  4. waitover a period of 3 hours
  5. customThe reaction was then quenched with MeOH (5 mL)
  6. concentrationconcentrated
  7. customPurification by chromatography on silica gel

Sources & evidence

ORD record
ord-4c1ce2b0d2ed46d7959037d84d81011a
Source dataset
uspto-grants-2014_08
Patent number
US08796310B2

Reaction notes

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