Diisopropylethylamine → HCID 23729230, compound

HRID 1676140Notes

Reaction equation

HRID 1676140 reaction equation
[NH2:1][CH2:2][CH:3]([OH:29])[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[S:19][CH:20]=[C:21]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:22]=3[CH3:23])[O:15][N:14]=2)=[CH:8][C:7]=1[CH3:28].[C:30]([N:37]([CH2:39][C:40](O)=[O:41])C)(OC(C)(C)C)=O.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>[OH:29][CH:3]([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[S:19][CH:20]=[C:21]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:22]=3[CH3:23])[O:15][N:14]=2)=[CH:8][C:7]=1[CH3:28])[CH2:2][NH:1][C:40](=[O:41])[CH2:39][NH:37][CH3:30]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 83692Glycine, N-[(1,1-dimethylethoxy)carbonyl]-N-methyl-HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59497867HCID 59497867, compound

Product 1

HCID 23729230HCID 23729230, compoundYield 75.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of rac-1-amino-3-{4-[5-(4-isobutyl-3-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propan-2-ol (100 mg, 0.241 mmol) in DCM (1 mL) is added to a stirred solution of Boc-sarcosine (60 mg, 0.317 mmol), DIPEA (38 mg, 0.292 mmol) and TBTU (85 mg, 0.265 mmol) in DCM (5 mL). The mixture is stirred at rt for 1 h, diluted with DCM (50 mL) and washed with sat. aq. Na2CO3 (2×20 mL). The organic extract is dried (Na2SO4), filtered and evaporated. The residue dissolved in 4M HCl in dioxane (10 mL) and stirred for 1 h. The mixture is diluted with DCM (75 mL) and washed with 1 N aq. NaOH (50 mL). The aq. phase is extracted with DCM (3×30 mL). The combined organic extracts are dried (Na2SO4), filtered and evaporated. The residue is purified on prep. TLC plates with DCM containing 10% of 7 N NH3 in MeOH to give rac-N-(2-hydroxy-3-{4-[5-(4-isobutyl-3-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propyl)-2-methylamino-acetamide (89 mg) as a white powder; LC-MS: tR=0.89 min, [M+1]=487.26; 1H NMR (D6-DMSO): δ 7.85 (t, J=6 Hz, 1H), 7.70 (s, 2H), 7.65 (s, 1H), 5.27 (d br, J=5 Hz, 1H), 3.93-3.85 (m, 1H), 3.76-3.65 (m, 2H), 3.43-3.35 (m, 1H), 3.24-3.14 (m, 1H), 3.02 (s, 2H), 2.54 (s, 3H), 2.45 (d, J=6.4 Hz, 2H), 2.30 (s, 6H), 2.20 (s, 3H), 1.83 (hept, J=7.0 Hz, 1H), 0.88 (d, J=7.0 Hz, 6H).

Workup

  1. washwashed with sat. aq. Na2CO3 (2×20 mL)
  2. extractionThe organic extract
  3. dry with materialis dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe residue dissolved in 4M HCl in dioxane (10 mL)
  7. stirringstirred for 1 h
  8. additionThe mixture is diluted with DCM (75 mL)
  9. washwashed with 1 N aq. NaOH (50 mL)
  10. extractionThe aq. phase is extracted with DCM (3×30 mL)
  11. dry with materialThe combined organic extracts are dried (Na2SO4)
  12. filtrationfiltered
  13. customevaporated
  14. customThe residue is purified on prep

Sources & evidence

ORD record
ord-58455ac4340d493590150b157beba794
Source dataset
uspto-grants-2011_08
Patent number
US08003800B2

Reaction notes

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