Formaldehyde → 7-(4-Bromo-2-chlorophenylamino)-8-chloro-3-piperidin-1-ylmethylimidazo[1,2-a]pyridine-6-carboxylic acid (2-hydroxyethoxy) amide

HRID 494709

Reaktionsgleichung

Reaktionsgleichung von HRID 494709
[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:7]=O.O.[OH:10][CH2:11][CH2:12][O:13][NH:14][C:15]([C:17]1[C:18]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([Br:34])=[CH:30][C:29]=2[Cl:35])=[C:19]([Cl:26])[C:20]2[N:21]([CH:23]=[CH:24][N:25]=2)[CH:22]=1)=[O:16]>CC#N.CCOC(C)=O.[O-]S(C(F)(F)F)(=O)=O.[Sc+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>[OH:10][CH2:11][CH2:12][O:13][NH:14][C:15]([C:17]1[C:18]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([Br:34])=[CH:30][C:29]=2[Cl:35])=[C:19]([Cl:26])[C:20]2[N:21]([C:23]([CH2:7][N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:24][N:25]=2)[CH:22]=1)=[O:16]

Komponenten

8

Edukt 4

HCID 712Formaldehyde2×HCID 962WaterHCID 8082Piperidine2×HCID 117195477-(4-Bromo-2-chlorophenylamino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylic acid (2-hydroxyethoxy)-amide

Produkt 1

HCID 116282497-(4-Bromo-2-chlorophenylamino)-8-chloro-3-piperidin-1-ylmethylimidazo[1,2-a]pyridine-6-carboxylic acid (2-hydroxyethoxy) amideAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 2734571Scandium(III) triflateKatalysator2×HCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Compound 39 was prepared by a modification of the procedure of T. Kercher et al. (manuscript in preparation). Piperidine (4 μL, 0.043 mmol) and 37% aqueous formaldehyde (5 μL, 0.065 mmol) were dissolved in 6:1 MeCN:water (0.5 ml), and stirred 30 minutes. 7-(4-bromo-2-chlorophenylamino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylic acid (2-hydroxyethoxy)amide (33a) (10 mg, 0.022 mmol) was added followed by scandium triflate (1 mg, 0.002 mmol). After stirring 16 hours, additional scandium triflate (1 mg), piperidine (3.8 μL) and aqueous formaldehyde (3.8 μL) were added. After about 60 hours, the reaction mixture was diluted with EtOAc and washed with water, 10% K2CO3, and brine. The organic layer was dried (Na2SO4) and concentrated. Purification by flash column chromatography using the Biotage system (40:1 CH2Cl2/MeOH to 20:1 CH2Cl2:MeOH to 9:1 CH2Cl2/MeOH) provided the desired product (39) as a white solid (6 mg, 50%). MS APCI (+) m/z 556, 558, 560 (M+, Cl, Br pattern) detected. 1H NMR (400 MHz, CD3OD) δ 8.83 (s, 1H), 7.56 (s, 1H), 7.54 (s, 1H), 7.27 (dd, 1H), 6.56 (d, 1H), 3.91 (m, 4H), 3.70 (m, 2H), 2.51 (broad s, 4H), 1.60 (broad s, 4H), 1.50 (broad s, 2H).

Aufarbeitung

  1. customCompound 39 was prepared by a modification of the procedure of T
  2. customKercher et al. (manuscript in preparation)
  3. waitAfter about 60 hours
  4. washwashed with water, 10% K2CO3, and brine
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-268679b947d54fa5ac3dc8060e341eac
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07538120B2

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