Methyl iodide → HCID 10238398, compound

HRID 1610998Notes

Reaction equation

HRID 1610998 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH2:20][O:21][C:22]1[C:27]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[Cl:36])=[CH:26][CH:25]=[CH:24][C:23]=1[CH:37]([OH:41])[C:38]([OH:40])=[O:39].CI>C1COCC1.CN1C(=O)N(C)CCC1>[Cl:36][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[CH:29]([O:28][C:27]1[C:22]([O:21][CH2:20][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[Cl:13])=[C:23]([CH:37]([OH:41])[C:38]([OH:40])=[O:39])[CH:24]=[CH:25][CH:26]=1)[CH3:1]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 9932554HCID 9932554, compoundHCID 178418339Butyllithium

Product 1

HCID 10238398HCID 10238398, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of diisopropylamine (170 μL, 1.21 mmol) under argon at −5° C. in THF (3 mL) was added n-butyllithium solution (483 μL, 2.5 M in hexanes, 1.21 mmol). After 15 min, the reaction mixture was cooled to −78° C. and a solution of Example 1 Part B compound (248 mg, 0.537 mmol) in THF (1 mL) was then added over 2 min. After an additional 15 min, DMPU was added (2 mL) and then methyl iodide (42 μL, 0.68 mmol). The reaction mixture was stirred for 2 h and then warmed to −40° C. After 14 h, the reaction was quenched with sodium hydroxide solution (1 M), warmed to room temperature and stirred for 1 h. The reaction mixture was acidified with 5% potassium hydrogen sulfate, extracted with CH2Cl2, dried (MgSO4) and evaporated. Purification by reverse phase preparative HPLC (YMC S5 ODS 20×250 mm column, acetonitrile/water−0.1% TFA gradient) provided the title compound, a colorless oil, as a 1:1 mixture of diastereomers, 75 mg (31% yield). LC/MS gave the correct molecular ion [(M+H)+=447] for the desired compound.

Workup

  1. waitAfter an additional 15 min
  2. temperaturewarmed to −40° C
  3. waitAfter 14 h
  4. customthe reaction was quenched with sodium hydroxide solution (1 M)
  5. temperaturewarmed to room temperature
  6. stirringstirred for 1 h
  7. extractionextracted with CH2Cl2
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customPurification by reverse phase preparative HPLC (YMC S5 ODS 20×250 mm column, acetonitrile/water−0.1% TFA gradient)

Sources & evidence

ORD record
ord-09347c64f89a48f8a9f38e7edb0afe3c
Source dataset
uspto-grants-2006_01
Patent number
US06984645B2

Reaction notes

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