Sodium Hydroxide → 4-(1-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoic acid

HRID 1410014Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1410014
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:39]=[CH:38][S:37][C:14]=3[N:15]=[C:16]([N:18]3[CH2:22][CH2:21][CH:20]([NH:23][C:24]([C:26]4[CH:35]=[CH:34][C:29]([C:30]([O:32]C)=[O:31])=[C:28]([OH:36])[CH:27]=4)=[O:25])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[OH-].[Na+]>C1COCC1.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:39]=[CH:38][S:37][C:14]=3[N:15]=[C:16]([N:18]3[CH2:22][CH2:21][CH:20]([NH:23][C:24]([C:26]4[CH:35]=[CH:34][C:29]([C:30]([OH:32])=[O:31])=[C:28]([OH:36])[CH:27]=4)=[O:25])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Komponenten

5

Edukt 2

HCID 14798Sodium HydroxideHCID 68379322Methyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoate

Produkt 1

HCID 665515464-(1-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoic acidAusbeute 14 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a stirred solution of methyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoate in 5 mL of THF and 5 mL of methanol was added a solution of 1N NaOH (5 mL) at room temperature. After the addition, the reaction was stirred at this temperature for 16 hours. The solvent was evaporated and the residue was diluted with water and adjusted to pH=2 by HCl (aq.). The suspension was filtered and dried. The crude was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 45% acetonitrile/55% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoic acid (15 mg, 14% over two steps). 1H NMR (300 MHz, DMSO): δ 9.72 (s, 1H), 8.85 (s, 1H), 8.76 (d, 1H, J=6.0 Hz), 7.86 (s, 1H), 7.84 (s, 1H), 7.43-7.37 (m, 3H), 6.92 (d, 1H, J=8.4 Hz), 4.56 (brs, 1H), 3.77-3.73 (m, 11H), 2.27-2.23 (m, 1H), 2.09-2.07 (m, 1H). LC-MS: 537 [M+H]+, tR=1.37 min. HPLC: 99.62% at 214 nm, 99.22% at 254 nm, tR=3.53 min.

Aufarbeitung

  1. additionAfter the addition
  2. customThe solvent was evaporated
  3. additionthe residue was diluted with water
  4. filtrationThe suspension was filtered
  5. customdried
  6. customThe crude was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm
  7. wait20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 45% acetonitrile/55% water (0.1% TFA V/V) in a linear fashion after just 9 min.

Quellen und Nachweise

ORD-Eintrag
ord-0a372c8c84dd4903814dc4350e6c8090
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921383B2

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