Diisopropylethylamine → Methyl 2-[4-((2S)-2-(acetylamino)-3-[4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoylamino)butoxy]-6-hydroxybenzoate

HRID 724639Notes

Reaction equation

HRID 724639 reaction equation
C([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]2[S:24](=[O:26])(=[O:25])[N:23](C(C)(C)C)[C:22](=[O:31])[CH2:21]2)=[CH:16][CH:15]=1)[C:10](O)=[O:11])=O)(C)(C)C.[CH:32](N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.Cl.[NH2:66][CH2:67][CH2:68][CH2:69][CH2:70][O:71][C:72]1[CH:81]=[CH:80][CH:79]=[C:78]([OH:82])[C:73]=1[C:74]([O:76][CH3:77])=[O:75]>CN(C)C=O>[C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]2[S:24](=[O:26])(=[O:25])[NH:23][C:22](=[O:31])[CH2:21]2)=[CH:16][CH:15]=1)[C:10]([NH:66][CH2:67][CH2:68][CH2:69][CH2:70][O:71][C:72]1[CH:81]=[CH:80][CH:79]=[C:78]([OH:82])[C:73]=1[C:74]([O:76][CH3:77])=[O:75])=[O:11])(=[O:5])[CH3:32]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11568707(2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(2-tert-butyl-1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoic acidHCID 69597617Methyl 2-(4-aminobutoxy)-6-hydroxybenzoate hydrochloride

Product 1

HCID 58746475Methyl 2-[4-((2S)-2-(acetylamino)-3-[4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoylamino)butoxy]-6-hydroxybenzoateYield 20.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(2-tert-butyl-1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoic acid (12 mg, 0.035 mmol) in N,N-dimethylformamide (1.0 mL,) was added N,N-diisopropylethylamine (0.018 mL, 0.10 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (16 mg, 0.042 mmol) and premixed for 5 minutes. Methyl 2-(4-aminobutoxy)-6-hydroxybenzoate hydrochloride (12 mg, 0.042 mmol) was added and the mixture was stirred for 2 h. The product was purified by preparative LCMS to afford the desired product (4.0 mg, 20%). 1H NMR (500 MHz, CD3OD): δ 7.43–7.45 (m, 2H), 7.35–7.36 (m, 2H), 7.27(t, J=8.3 Hz), 6.49–6.53 (m, 2H), 5.12–5.17 (m, 1H), 4.55–4.59 (m, 1H), 3.96–3.99 (m, 2H), 3.90 (s, 3H), 2.89–3.89 (m, 4H), 1.95 (s, 3H), 1.64–1.68 (m, 2H), 1.57–1.61 (m, 2H); LCMS found for C26H32N3O9S (M+H)+: m/z=562.2.

Workup

  1. additionpremixed for 5 minutes
  2. customThe product was purified by preparative LCMS

Sources & evidence

ORD record
ord-b854c4804f49489b82fb2939357a693c
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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