Sodium hydride → HCID 25105909, compound

HRID 1042074Notes

Reaction equation

HRID 1042074 reaction equation
[NH2:1][C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[N:5]=[C:4]([CH3:11])[C:3]=1[C:12]#[C:13][CH:14]([CH:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[OH:15].[H-].[Na+].Br[CH2:24][C:25]([O:27]C(C)(C)C)=[O:26]>CN(C)C=O>[NH2:1][C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[N:5]=[C:4]([CH3:11])[C:3]=1[C:12]#[C:13][CH:14]([O:15][CH2:24][C:25]([OH:27])=[O:26])[CH:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 25105745HCID 25105745, compound

Product 1

HCID 25105909HCID 25105909, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of Example 35B (20 mg, 0.074 mmol) in 0.5 mL of anhydrous N,N-dimethylformamide was added NaH (60%, 4.0 mg, 0.096 mmol). The resulting mixture was stirred for 20 min before tert-butyl bromoacetate (11 μL, 0.0.74 mmol) was added, and stirring continued for 2 h. The reaction mixture was then partitioned between ethyl acetate (10 mL) and brine (10 mL), the organic layer was dried over MgSO4, filtered, evaporated to dryness in vacuuo. The residue was treated with 1.0 mL of 4N HCl in 1,4-dioxane for 3 h. Organic solvent was then removed on a rotavap, and the residue was purified using reverse phase HPLC (C-18 column, eluting with a 5-100% CH3CN gradient in 10 mM ammonium acetate(aq.)) to give the title Compound (5 mg, 21% yield). 1H NMR (300 MHz, DMSO-d6) δ 8.45 (s, 1H), 8.15 (brs, 2H), 4.79-4.60 (m, 2H), 4.34 (d, J=7.1 Hz, 1H), 2.54 (s, 3H), 2.25-2.15 (m, 1H), 1.81-1.38 (m, 8H). MS (ESI) m/z 330 (M+H)+.

Workup

  1. additionwas added
  2. customThe reaction mixture was then partitioned between ethyl acetate (10 mL) and brine (10 mL)
  3. dry with materialthe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated to dryness in vacuuo
  6. additionThe residue was treated with 1.0 mL of 4N HCl in 1,4-dioxane for 3 h
  7. customOrganic solvent was then removed on a rotavap
  8. customthe residue was purified
  9. washeluting with a 5-100% CH3CN gradient in 10 mM ammonium acetate(aq.))

Sources & evidence

ORD record
ord-32a7ca78e443448ca0fbddc80c9ae543
Source dataset
uspto-grants-2013_10
Patent number
US08557828B2

Reaction notes

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