Water → Dasatinib Carboxylic Acid

HRID 1437117

Reaktionsgleichung

Reaktionsgleichung von HRID 1437117
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10]([C:12]1[S:16][C:15]([NH:17][C:18]2[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]3[CH2:30][CH2:29][N:28]([CH2:31][C:32]([O:34]CC)=[O:33])[CH2:27][CH2:26]3)[CH:19]=2)=[N:14][CH:13]=1)=[O:11].[OH-].[Na+].O>CO>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10]([C:12]1[S:16][C:15]([NH:17][C:18]2[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]3[CH2:30][CH2:29][N:28]([CH2:31][C:32]([OH:34])=[O:33])[CH2:27][CH2:26]3)[CH:19]=2)=[N:14][CH:13]=1)=[O:11]

Komponenten

5

Edukt 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 57940725Dasatinib Carboxylic Acid Ethyl Ester

Produkt 1

HCID 11854012Dasatinib Carboxylic AcidAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

A mixture of ethyl 2-(4-(6-(5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-ylamino)-2-methylpyrimidin-4-yl)piperazin-1-yl)acetate (4) (0.21 g, 0.40 mmol) in 10 mL of MeOH was added 1.0 N NaOH (2.4 mL, 2.4 mmol) at rt. The mixture was stirred at rt for 1 h to become a clear solution. The HPLC indicated the reaction was complete with a single peak with Rt 2.417 min. The solvents in the solution were reduced to a small volume. The remaining liquid was treated with H2O (10 mL). The aqueous solution was washed with CH2Cl2 (2×10 mL) and then adjusted to pH 6-7 with 1 N HCl (2.4 mL) to result in white precipitation. The solid was collected on a filter, washed with water to give 0.18 g of 2-(4-(6-(5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-ylamino)-2-methylpyrimidin-4-yl)piperazin-1-yl)acetic acid (IV) (90% yield). HPLC>99% pure. LC/MS (ES+) 502/504 (M+H, 100), HRMS calcd for C22H24ClN7O3S 502.1428, found 502.1413.1H NMR (DMSO-d6) δ 11.49 (br s, 1H), 9.89 (s, 1H), 8.23 (s, 1H), 7.41(dd, J=7.5, 1.6 Hz, 1H), 7.28 (m, 2H), 6.07 (s, 1H), 3.55 (s, 4H0, 3.19 (s, 2H), 2.61 (t, J=4.7 Hz, 4H), 2.42 (s, 3H), 2.24 (s, 3H). Anal. Calcd for C22H24ClN7O3S 0.85H2O: C, 51.08; H, 5.01; Cl, 6.85; N, 18.95; S, 6.20; H2O, 2.96%. Found: C, 51.23; H, 4.97; Cl, 7.08; N, 19.09; S, 5.92; H2O, 2.94%.

Aufarbeitung

  1. washThe aqueous solution was washed with CH2Cl2 (2×10 mL)
  2. customto result in white precipitation
  3. customThe solid was collected on a filter
  4. washwashed with water

Quellen und Nachweise

ORD-Eintrag
ord-3e6fafa780a942bca9419eed3e6eb035
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07622473B2

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