Glycolic Acid → HCID 24752895, compound

HRID 2065913Notes

Reaction equation

HRID 2065913 reaction equation
[NH2:1][CH2:2][CH:3]([OH:30])[CH2:4][O:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([C:13]2[N:17]=[C:16]([C:18]3[CH:19]=[N:20][C:21]([O:25][CH:26]([CH3:28])[CH3:27])=[C:22]([Cl:24])[CH:23]=3)[O:15][N:14]=2)=[CH:8][C:7]=1[CH3:29].[C:31](O)(=[O:34])[CH2:32][OH:33].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl.CC(=O)OCC>[Cl:24][C:22]1[CH:23]=[C:18]([C:16]2[O:15][N:14]=[C:13]([C:9]3[CH:10]=[C:11]([CH3:12])[C:6]([O:5][CH2:4][CH:3]([OH:30])[CH2:2][NH:1][C:32](=[O:33])[CH2:31][OH:34])=[C:7]([CH3:29])[CH:8]=3)[N:17]=2)[CH:19]=[N:20][C:21]=1[O:25][CH:26]([CH3:27])[CH3:28]

Participants

7

Reactant 4

HCID 757Glycolic AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59392496HCID 59392496, compound

Product 1

HCID 24752895HCID 24752895, compoundYield 14.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (RS)-1-amino-3-{4-[5-(5-chloro-6-isopropoxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propan-2-ol (313 mg, 0.6 mmol) in DCM (10 mL), glycolic acid (95 mg, 1.25 mmol) and Hünig's base (233 mg, 1.8 mmol) are added. The mixture is cooled to 0° C. and TBTU (236 mg, 0.74 mmol) is added. The mixture is stirred at 0° C. for 1 h, then at rt for 16 h before it is diluted with EA (250 mL), washed with 1N aq. NaOH solution (3×25 mL), 1N aq. KHSO4 (25 mL) and brine (25 mL), dried over Na2SO4, filtered and concentrated. The crude product is purified by prep. HPLC to give N—((RS)-3-{4-[5-(5-chloro-6-isopropoxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide (42 mg) as a white powder; LC-MS: tR=1.06 min; [M+1]+=491.48; 1H NMR (CD3OD) δ 1.45 (d, J=6.3 Hz, 6H), 2.38 (s, 6H), 3.47 (dd, J=13.6, 7.3 Hz, 1H), 3.66 (dd, J=13.6, 4.5 Hz, 1H), 3.87 (m, 2H), 4.04 (s, 2H), 4.14 (m, 1H), 5.52 (m, 1H), 7.78 (s, 2H), 8.43 (s, 1H), 8.85 (s, 1H)

Workup

  1. washwashed with 1N aq. NaOH solution (3×25 mL), 1N aq. KHSO4 (25 mL) and brine (25 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-0df738e99deb4733b6ad3ac18533658c
Source dataset
uspto-grants-2012_10
Patent number
US08288554B2

Reaction notes

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