Diisopropylethylamine → 2-(4-((S)-1,2-Dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamido)succinamide

HRID 2271400

Reaktionsgleichung

Reaktionsgleichung von HRID 2271400
[OH:1][C@@H:2]([C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[N:8]=[C:7]([C:25](O)=[O:26])[CH:6]=1)[CH2:3][OH:4].[NH2:28][C@@H:29]([CH2:33][C:34]([NH2:36])=[O:35])[C:30]([NH2:32])=[O:31].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:1][C@@H:2]([C:5]1[CH:10]=[C:9]([C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)=[CH:15][CH:16]=2)[N:8]=[C:7]([C:25]([NH:28][CH:29]([CH2:33][C:34]([NH2:36])=[O:35])[C:30]([NH2:32])=[O:31])=[O:26])[CH:6]=1)[CH2:3][OH:4]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 447212AsparaginamideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66668271(S)-4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinic acid

Produkt 1

HCID 867065772-(4-((S)-1,2-Dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamido)succinamideAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of (S)-4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinic acid (assume 0.44 mmol) in DMF (5 mL) was added (S)-2-aminosuccinamide (0.076 g, 0.45 mmol), DIEA (0.20 mL, 1.1 mmol) and HBTU (0.203 g, 0.54 mmol). The reaction was stirred overnight then partitioned between 50 mL EtOAc and 50 mL brine. The aqueous layer was extracted once more with 25 mL EtOAc and combined. The organics were dried over Na2SO4, filtered and evaporated in vacuo. The residue was crystallized from 4 mL warm acetone, the solid filtered off, rinsed with additional acetone and dried under vacuum at 50° C. to yield the product S)-2-(4-((S)-1,2-Dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamido)succinamide as a light tan powder (0.125 g, 0.26 mmol, 59% yield, LC/MS: m/z=483.1 [M+H]+, 1H NMR (400 MHz, DMSO-d6): δ 9.29 (d, J=8.4 Hz, 1H), 8.25 (d, J=8.8 Hz, 2H), 8.06 (s, 1H), 7.99 (s, 1H), 7.48 (s, 1H), 7.40 (s, 1H), 7.32-7.25 (m, 2H), 7.21-7.15 (m, 2H), 7.14-7.07 (m, 3H), 6.99 (s, 1H), 5.64 (d, J=4.8 Hz, 1H), 4.85 (t, J=6.0 Hz, 1H), 4.75-4.64 (m, 2H), 3.62-3.49 (m, 2H), 2.79-2.70 (m, 1H), 2.61-2.53 (m, 1H).

Aufarbeitung

  1. customthen partitioned between 50 mL EtOAc and 50 mL brine
  2. extractionThe aqueous layer was extracted once more with 25 mL EtOAc
  3. dry with materialThe organics were dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was crystallized from 4 mL
  7. temperaturewarm acetone
  8. filtrationthe solid filtered off
  9. washrinsed with additional acetone
  10. customdried under vacuum at 50° C.

Quellen und Nachweise

ORD-Eintrag
ord-7557bcb9eb7240a4b49a3cda6f1f7d0e
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09120752B2

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