Lithium diisopropylamide → HCID 67432981, compound

HRID 1040202Notes

Reaction equation

HRID 1040202 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]2[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[CH:5]=[C:6]([C:8]2[S:12][CH:11]=[N:10][CH:9]=2)[CH:7]=1.[Li+].CC([N-]C(C)C)C.[CH3:32][C:33]1([CH3:44])[C:42](=[O:43])[CH2:41][CH2:40][CH2:39][C:34]21[O:38][CH2:37][CH2:36][O:35]2>C1COCC1.[Cl-].[NH4+]>[CH3:32][C:33]1([CH3:44])[C:42]([C:11]2[S:12][C:8]([C:6]3[CH:5]=[C:4]([NH:13][C:14]4[N:19]=[C:18]([C:20]([F:21])([F:23])[F:22])[CH:17]=[CH:16][N:15]=4)[CH:3]=[C:2]([CH3:1])[CH:7]=3)=[CH:9][N:10]=2)([OH:43])[CH2:41][CH2:40][CH2:39][C:34]21[O:35][CH2:36][CH2:37][O:38]2

Participants

6

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 109977176,6-dimethyl-1,4-dioxaspiro[4.5]decan-7-oneHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 67432981HCID 67432981, compoundYield 57.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

To a stirred solution of INTERMEDIATE 4 (1.09 g, 3.24 mmol) in THF (17 mL) was added LDA (2M, 4.86 mL, 9.72 mmol) dropwise at −78° C. The orange solution was left to stir for 30 min at that temperature, treated with 6,6-dimethyl-1,4-dioxaspiro[4.5]decan-7-one (0.72 g, 3.9 mmol) in THF (4.5 mL) dropwise, and allowed to warm to room temperature as the bath did. The reaction mixture was diluted with saturated ammonium chloride solution, and extracted with EtOAc (3×). The combined organics were washed with brine, dried (sodium sulfate), filtered concentrated, and purified by column chromatography on silica to afford 6,6-dimethyl-7-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decan-7-ol (964 mg, 1.85 mmol) as a light yellow foam. MS ESI: [M+H]+ m/z 521.1.

Workup

  1. waitThe orange solution was left
  2. extractionextracted with EtOAc (3×)
  3. washThe combined organics were washed with brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography on silica

Sources & evidence

ORD record
ord-9d45d762adf94cb690d67d9e4cc19925
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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