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

HRID 494709

反応式

HRID 494709 の反応式
[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]

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 2734571Scandium(III) triflate触媒2 回HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-268679b947d54fa5ac3dc8060e341eac
出典データセット
uspto-grants-2009_05
特許番号
US07538120B2

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