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

HRID 494709

반응식

HRID 494709 반응식
[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]

참가 물질

8

반응물 4

HCID 712Formaldehyde2회HCID 962WaterHCID 8082Piperidine2회HCID 117195477-(4-Bromo-2-chlorophenylamino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylic acid (2-hydroxyethoxy)-amide

생성물 1

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

시약·촉매·용매 3

HCID 2734571Scandium(III) triflate촉매2회HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-268679b947d54fa5ac3dc8060e341eac
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07538120B2

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