Lithium diisopropylamide → HCID 67261191, compound

HRID 1040061Notes

Reaction equation

HRID 1040061 reaction equation
[Li+].CC([N-]C(C)C)C.[CH:9]1([C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[CH:25]=[C:24]([C:26]4[S:30][CH:29]=[N:28][CH:27]=4)[CH:23]=[C:22]([F:31])[CH:21]=3)[N:13]=2)[CH2:11][CH2:10]1.[C:32]([Si:36]([CH3:43])([CH3:42])[O:37][CH2:38][C:39]([CH3:41])=[O:40])([CH3:35])([CH3:34])[CH3:33]>O1CCCC1>[Si:36]([O:37][CH2:38][C:39]([C:29]1[S:30][C:26]([C:24]2[CH:23]=[C:22]([F:31])[CH:21]=[C:20]([NH:19][C:14]3[N:13]=[C:12]([CH:9]4[CH2:11][CH2:10]4)[C:17]([F:18])=[CH:16][N:15]=3)[CH:25]=2)=[CH:27][N:28]=1)([OH:40])[CH3:41])([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:43])[CH3:42]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 41249691-(tert-Butyldimethylsilyloxy)-2-propanoneHCID 672579164-cyclopropyl-5-fluoro-N-[3-fluoro-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine

Product 1

HCID 67261191HCID 67261191, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

LDA (0.757 mL, 1.362 mmol) was added to tetrahydrofuran (4 mL) at −78° C. After 15 minutes at −78° C., a solution of the product of Step 4 (150 mg, 0.454 mmol) in tetrahydrofuran (4 mL) was added dropwise. After 30 minutes at −78° C., a solution of 1-{[tert-butyl(dimethyl)-silyl]oxy}acetone (0.110 mL, 0.568 mmol) in tetrahydrofuran (4 mL) was added dropwise at −78° C. The reaction mixture was allowed to warm to ambient temperature. After 1 hour, the reaction mixture was quenched with saturated ammonium chloride, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate and hexanes to afford 1-{[tert-butyl(dimethyl)silyl]oxy}-2-(5-{3-[(4-cyclopropyl-5-fluoropyrimidin-2-yl)amino]-5-fluorophenyl}-1,3-thiazol-2-yl)propan-2-ol (150 mg, 0.29 mmol, 64%). MS ESI: [M+H]+ m/z 519.2.

Workup

  1. waitAfter 30 minutes at −78° C.
  2. waitAfter 1 hour
  3. customthe reaction mixture was quenched with saturated ammonium chloride
  4. additiondiluted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silica gel
  10. washeluting with ethyl acetate and hexanes

Sources & evidence

ORD record
ord-755805cac8f74836836e816b10bd3ff3
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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