HCID 10457720, compound → HCID 10073731, compound

HRID 1294731Notes

Reaction equation

HRID 1294731 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:10]=[C:11]([C@H:15]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)[C:16]3[CH:28]=[CH:27][C:19]([C:20]([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[O:21])=[CH:18][CH:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:6][CH:7]=1>CO>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:10]=[C:11]([C@@H:15]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)[C:16]3[CH:28]=[CH:27][C:19]([C:20]([N:22]([CH2:23][CH3:24])[CH2:25][CH3:26])=[O:21])=[CH:18][CH:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 1

HCID 10457720HCID 10457720, compound

Product 1

HCID 10073731HCID 10073731, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of INTERMEDIATE 5a (103 mg) in toluene (2 mL) was added 3-chloro-bromobenzene (34 μL; 1.3 eq), Pd2(dba)3 (8.2 g; 0.04 eq), Sodium tert-butoxide (29 g; 1.4 eq) and BINAP (11 g; 0.08 eq). The solution was heated in the microwave in a sealed tube for 5 min at 110° C. The resulting mixture filtered through celite and concentrated. The crude was purified by a normal phase MPLC with a disposable silica gel column (40 g); eluting 40% to 60% ethyl acetate in hexane. Pure fraction collected and concentrated to afford yellow foam. The resulting product was dissolved in dichloromethane (5 mL) and trifluoroacetic acid (0.5 mL) was added and the solution stirred for 18 hours until complete removal of the boc group. The reaction was concentrated and diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate. The aqueous was extracted with two portions of dichloromethane and the combined organics were dried over anhydrous sodium sulfate, filtered and concentrated to about 2 mL of solvent. In the solution was added 560 μL of 1M HCl in ether and the solvent was removed and the product was isolated as the hydrochloride salt to give COMPOUND 30 (77 mg, 73% yield) as beige solid. Purity (HPLC): >99%; Optical purity (Chiral HPLC): >99%; 1H NMR (400 MHz, CD3OD) 1.07 (t, J=6.40 Hz, 3H), 1.20 (t, J=6.64 Hz, 3H), 3.05-3.27 (m, 6H), 3.43-3.57 (m, 6H), 6.80 (dd, J=8.01, 1.27 Hz, 1H), 6.92 (dd, J=8.15, 1.51 Hz, 1H), 6.99 (t, J=2.00 Hz, 1H), 7.00-7.04 (m, 1H), 7.13-7.17 (m, 2H), 7.27 (t, J=7.76 Hz, 1H), 7.39 (br s, 1H), 7.41 (d, J=7.81 Hz, 2H), 7.75 (d, J=6.74 Hz, 2H). [a]D20=+20.77 deg [c 0.467, MeOH].

Sources & evidence

ORD record
ord-3bb4639edf5c439c99e3b721d48eef77
Source dataset
uspto-grants-2007_07
Patent number
US07241764B2

Reaction notes

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