Lithium diisopropylamide → N-[1-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutyl]-2-methylpropane-2-sulfinamide

HRID 1040070Notes

Reaction equation

HRID 1040070 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11]3[CH:16]=[C:15]([C:17]4[S:21][CH:20]=[N:19][CH:18]=4)[CH:14]=[C:13]([CH3:22])[CH:12]=3)[N:5]=2)[CH2:3][CH2:2]1.[Li+].CC([N-]C(C)C)C.[C:31]1(=[N:35][S:36]([C:38]([CH3:41])([CH3:40])[CH3:39])=[O:37])[CH2:34][CH2:33][CH2:32]1>O1CCCC1>[CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11]3[CH:16]=[C:15]([C:17]4[S:21][C:20]([C:31]5([NH:35][S:36]([C:38]([CH3:41])([CH3:40])[CH3:39])=[O:37])[CH2:32][CH2:33][CH2:34]5)=[N:19][CH:18]=4)[CH:14]=[C:13]([CH3:22])[CH:12]=3)[N:5]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 584561394-cyclopropyl-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amineHCID 67250305N-cyclobutylidene-2-methylpropane-2-sulfinamide

Product 1

HCID 67247850N-[1-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutyl]-2-methylpropane-2-sulfinamideYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of the product of Step 1 (250 mg, 0.81 mmol) in tetrahydrofuran (5.0 mL) at −78° C. was added LDA (1.62 mL, 2.0 M, 3.24 mmol). The mixture was stirred for 15 min at −78° C. N-cyclobutylidene-2-methylpropane-2-sulfinamide (169 mg, 0.97 mmol) in tetrahydrofuran (3 mL) was added dropwise at −78° C. and the reaction was allowed to warm to room temperature and stirred over 2 h. The mixture was quenched with aqueous ammonium chloride and the mixture was extracted with ethyl acetate (3×200 mL). The combined organic fractions were washed with brine, dried over sodium sulfate, filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (0-100% ethyl acetate in hexanes) provided 182 mg (0.38 mmol, 47%) of N-[1-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutyl]-2-methylpropane-2-sulfinamide. MS ESI: [M+H]+ m/z 482.2.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred over 2 h
  3. customThe mixture was quenched with aqueous ammonium chloride
  4. extractionthe mixture was extracted with ethyl acetate (3×200 mL)
  5. washThe combined organic fractions were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel (0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-6aacdc413f104e518cb43fd77917e90b
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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