Diisopropylethylamine → HCID 58746503, compound

HRID 724718Notes

Reaction equation

HRID 724718 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[S:27](=[O:29])(=[O:28])[NH:26][C:25](=[O:30])[CH2:24]2)=[C:19]([CH3:31])[CH:18]=1)[C:13](O)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:59][CH2:60][CH2:61][CH2:62][CH2:63][O:64][C:65]1[CH:74]=[CH:73][CH:72]=[C:71]([OH:75])[C:66]=1[C:67]([O:69][CH3:70])=[O:68].C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[S:27](=[O:29])(=[O:28])[NH:26][C:25](=[O:30])[CH2:24]2)=[C:19]([CH3:31])[CH:18]=1)[C:13]([NH:59][CH2:60][CH2:61][CH2:62][CH2:63][O:64][C:65]1[CH:74]=[CH:73][CH:72]=[C:71]([OH:75])[C:66]=1[C:67]([O:69][CH3:70])=[O:68])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11633706HCID 11633706, compoundHCID 11832643Methyl 2-(4-aminobutoxy)-6-hydroxybenzoate

Product 1

HCID 58746503HCID 58746503, compoundYield 57.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2S)-2-[(benzyloxy)carbonyl]amino-3-[4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)-3-methylphenyl]propanoic acid (85 mg, 0.19 mmol) in N,N-dimethylformamide (2.0 mL) were added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (88.4 mg, 0.200 mmol) at 0° C. under an atmosphere of nitrogen. After stirring for 15 min, methyl 2-(4-aminobutoxy)-6-hydroxybenzoate (54.7 mg, 0.228 mmol) and N,N-diisopropylethylamine (99.5 μL, 0.571 mmol) was added. The reaction mixture was warmed to room temperature for 1 h. The reaction was diluted with ethyl acetate and quenched with saturated sodium bicarbonate solution. The aqueous phase was extracted with EtOAc once. The combined organic solutions were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by preparative LCMS to yield the desired product (73 mg, 57%). 1H NMR (400 MHz, CD3OD): δ 8.00 (m, 1H), 7.38–7.15 (m, 9H), 6.48 (m, 2H), 5.45 (m, 1H), 5.03 (m, 2H), 4.30 (m, 1H), 3.94 (m, 2H), 3.85 (s, 3H), 3.3 (m, 4H), 3.02 (m, 1H), 2.87 (m, 1H), 2.42 (s, 3H), 1.6 (m, 4H); MF=C33H37N3O10S; LCMS found for C33H38N3O10S (M+H)+: m/z=668.

Workup

  1. customquenched with saturated sodium bicarbonate solution
  2. extractionThe aqueous phase was extracted with EtOAc once
  3. washThe combined organic solutions were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified by preparative LCMS

Sources & evidence

ORD record
ord-a6212a1076f84dcdb374347ceb418172
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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