Sodium hydride → HCID 11497618, compound

HRID 2104216Notes

Reaction equation

HRID 2104216 reaction equation
[H-].[Na+].[CH2:3]([O:7][C:8]1[CH:13]=[CH:12][C:11]([S:14]([NH:17][CH:18]([CH2:22][C:23]2[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([CH3:32])[CH:30]=3)[NH:25][CH:24]=2)[C:19]([OH:21])=[O:20])(=[O:16])=[O:15])=[CH:10][CH:9]=1)[C:4]#[C:5][CH3:6].[CH3:33][O:34][C:35]1[CH:42]=[CH:41][C:38]([CH2:39]Cl)=[CH:37][CH:36]=1>CN(C)C=O>[CH2:3]([O:7][C:8]1[CH:9]=[CH:10][C:11]([S:14]([NH:17][CH:18]([CH2:22][C:23]2[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([CH3:32])[CH:30]=3)[N:25]([CH2:39][C:38]3[CH:41]=[CH:42][C:35]([O:34][CH3:33])=[CH:36][CH:37]=3)[CH:24]=2)[C:19]([OH:21])=[O:20])(=[O:15])=[O:16])=[CH:12][CH:13]=1)[C:4]#[C:5][CH3:6]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 11676244HCID 11676244, compound

Product 1

HCID 11497618HCID 11497618, compoundYield 67.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 20 mL vial, NaH (60% in mineral oil) (0.033 g, 0.831 mmol) was added to a solution of 2-(4-but-2-ynyloxy-benzenesulfonylamino)-3-(5-methyl-1H-indol-3-yl)-propionic acid (Example 1) (0.100 g, 0.234 mmol) in anhydrous N,N-dimethylformamide (2 mL) at 0° C. The reaction mixture was placed in a shaker for 20 min. at 0° C. 4-Methoxy-benzyl chloride (0.032 mL, 0.234 mmol) was added to the solution and allowed to react for 10 hours at 0° C. The reaction mixture was quenched with H2O and acidified with HCl. The solution was extracted with EtOAc, washed with H2O and brine, dried over Na2SO4, and concentrated. The residue was purified by RP-HPLC to give 0.086 g (67%) of the title compound as a pale yellow solid. 1H NMR (DMSO-d6): 400 MHz δ 12.58 (bs, 1H), 8.09 (d, J=8.4 Hz, 1H), 7.53 (d, J=11.6 Hz, 2H), 7.20 (d, J=8.0 Hz, 1H), 7.09 (s, 1H), 7.07 (d, J=8.4 Hz, 2H), 7.00 (s, 1H), 6.92-6.80 (m, 5H), 5.17 (s, 2H), 4.76 (q, J=2.4 Hz, 2H), 3.82 (q, J=8.0 Hz, 1H), 3.69 (s, 3H), 3.00 (dd J=14.4, 6.8 Hz, 1H), 2.79 (dd J=14.4, 7.6 Hz, 1H), 2.32 (s, 3H), 1.82 (t, J=2.4 Hz, 3H); HRMS: calcd for C30H31N2O6S (ESI+, [M+H]1+), 547.1897; found 547.1896; LCMS m/z (ESI) [M−H] 545, retention time=2.76 min.

Workup

  1. customto react for 10 hours at 0° C
  2. customThe reaction mixture was quenched with H2O
  3. extractionThe solution was extracted with EtOAc
  4. washwashed with H2O and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by RP-HPLC

Sources & evidence

ORD record
ord-d2e77bf779864cb2b297dd0c0168fb63
Source dataset
uspto-grants-2009_08
Patent number
US07576222B2

Reaction notes

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