Potassium Hydroxide → (2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-1-tert-butoxycarbonyl-pyrrolidine-2-carboxylic acid

HRID 908435Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 908435
[OH-].[K+].[NH2:3][C:4]1[N:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][N:13]([C@H:15]3[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:17]([C:27]([O:29]C)=[O:28])[CH2:16]3)[CH:14]=2)=[CH:6][C:5]=1[C:31]1[O:32][C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=1>CO>[NH2:3][C:4]1[N:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][N:13]([C@H:15]3[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])[C@H:17]([C:27]([OH:29])=[O:28])[CH2:16]3)[CH:14]=2)=[CH:6][C:5]=1[C:31]1[O:32][C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=1

Komponenten

4

Edukt 2

HCID 14797Potassium HydroxideHCID 67388265(2S,4R)-O1-tert-butyl O2-methyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]pyrrolidine-1,2-dicarboxylate

Produkt 1

HCID 67389021(2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-1-tert-butoxycarbonyl-pyrrolidine-2-carboxylic acidAusbeute 47,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

(2S,4R)—O1-tert-butyl O2-methyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]pyrrolidine-1,2-dicarboxylate was prepared according to the procedure described in Example 26 except that caesium carbonate was used, using (2S,4S)—O1-tert-butyl O2-methyl 4-methylsulphonyloxypyrrolidine-1,2-dicarboxylate (Siddiqui et al., PCT. Int. Appl. US2007/0167426) as alkylating agent to give 442 mg of solid. NMR Spectrum: (CDCl3) 1.45 (s, 5.4H), 1.48 (s, 3.6H), 2.44-2.52 (m, 1H). 2.82-2.96 (m, 1H), 3.79 (s, 1.8H), 3.80 (s, 1.2H), 3.82-3.89 (m, 0.4H), 3.92-3.98 (m, 0.6H), 4.03-4.11 (m, 1H), 4.49-4.55 (m, 0.6H), 4.60-4.65 (m, 0.4H), 4.99-5.10 (m, 1H), 7.05 (bs, 2H), 7.35-7.42 (m, 2H), 7.59-7.63 (m, 1H), 7.68 (s, 1H), 7.74-7.78 (m, 1H), 7.81 (d, 1H), 8.35 (d, 1H), 8.40 (d, 1H) Mass spectrum: M+H+ 505 A solution of potassium hydroxide (1.249 ml, 2N) was added to (2S,4R)—O1-tert-butyl O2-methyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]pyrrolidine-1,2-dicarboxylate (420 mg) dissolved in methanol (10 ml) over a period of 10 minutes under argon. The resulting solution was stirred at 50° C. for 2 hours. The methanol was evaporated and the pH was adjusted to 5.5 with HCl 6N. The mixture was evaporated on reduce pressure. The reaction mixture was purified by preparative HPLC using a Waters X-Terra reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml/minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford (2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-1-tert-butoxycarbonyl-pyrrolidine-2-carboxylic acid (195 mg) as a solid. NMR Spectrum: (DMSOd6) 1.35 (s, 5.4H), 1.39 (s, 3.6H), 2.32-2.43 (m, 1H), 2.66-2.82 (m, 1H), 3.63-3.71 (m, 1H), 3.80-3.89 (m, 1H), 4.28-4.36 (m, 1H), 4.96-5.06 (m, 1H), 7.40-7.49 (m, 2H), 7.67 (bs, 2H), 7.77-7.81 (m, 1H), 7.82-7.86 (m, 1H), 7.97 (s, 1H), 8.36 (s, 0.6H), 8.39 (s, 0.4H), 8.41-8.46 (m, 1H), 8.50-8.55 (m, 1H); Mass spectrum: M+H+ 491

Aufarbeitung

  1. customThe methanol was evaporated
  2. customThe mixture was evaporated
  3. customThe reaction mixture was purified by preparative HPLC
  4. additionThe fractions containing the desired compound
  5. customwere evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-0ef49da54a244b8eb1515d841e9afe92
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08017611B2

Notizen zur Reaktion

Wird geladen…