Ammonium Acetate → (1S,2S,3R,4R)-3-[6-Bromo-2-(4-morpholin-4-ylmethyl-phenyl)-3H-imidazo[4,5-b]pyridin-7-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide

HRID 591965

反応式

HRID 591965 の反応式
[NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([NH:9][C@@H:10]2[C@@H:15]3[CH2:16][C@@H:12]([CH:13]=[CH:14]3)[C@@H:11]2[C:17]([NH2:19])=[O:18])[C:5]([Br:20])=[CH:4][N:3]=1.[N:21]1([CH2:27][C:28]2[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=2)[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.C([O-])(=O)C.[NH4+]>C(O)C>[Br:20][C:5]1[C:6]([NH:9][C@@H:10]2[C@@H:15]3[CH2:16][C@@H:12]([CH:13]=[CH:14]3)[C@@H:11]2[C:17]([NH2:19])=[O:18])=[C:7]2[N:8]=[C:32]([C:31]3[CH:30]=[CH:29][C:28]([CH2:27][N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[CH:35][CH:34]=3)[NH:1][C:2]2=[N:3][CH:4]=1

参加物

5

反応物 3

HCID 517165Ammonium AcetateHCID 27954984-[(Morpholin-4-yl)methyl]benzaldehydeHCID 117701905(1S,2S,3R,4R)-3-(2,3-Diamino-5-bromo-pyridin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide

生成物 1

HCID 178513973(1S,2S,3R,4R)-3-[6-Bromo-2-(4-morpholin-4-ylmethyl-phenyl)-3H-imidazo[4,5-b]pyridin-7-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

(1S,2S,3R,4R)-3-(2,3-Diamino-5-bromo-pyridin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (40.0 mg, 0.118 mmol), 4-morpholin-4-ylmethyl-benzaldehyde (26.7 mg, 0.130 mmol) and ammonium acetate (59.4 mg, 0.771 mmol) were heated in ethanol (5 mL) at 70° C. for 18 hours. The reaction mixture was concentrated and the product was purified by reverse phase chromatography (Gilson) to afford, following neutralization with saturated sodium bicarbonate solution and filtration, the title compound 35 mg (57%). mp: 217-219° C., 1H NMR (300 MHz, DMSO-d6): 13.27 (s, 1H), 8.10 (d, J=9 Hz, 2H), 8.03 (s, 1H), 7.76 (s, 1H), 7.48 (d, J=8 Hz, 2H), 7.22 (s, 1H), 7.16 (d, J=8 Hz, 1H), 6.41 (br s, 1H), 6.37 (br s, 1H), 5.23 (t, J=8 Hz, 1H), 3.59 (br s, 4H), 3.53 (s, 2H), 2.89 (s, 1H), 2.78 (s, 1H), 2.39 (br s, 4H), 2.25 (d, J=8 Hz, 1H), 1.90 (s, 1 h), 1.39 (d, J=8 Hz, 1H). MS: 523, 525 (M+H), HPLC: 1.82 min (G method).

後処理

  1. concentrationThe reaction mixture was concentrated
  2. customthe product was purified by reverse phase chromatography (Gilson)
  3. customto afford
  4. filtrationwith saturated sodium bicarbonate solution and filtration
  5. custom1.82 min (G method)

出典と根拠

ORDレコード
ord-8389e0b15098497c984d1ea7cc96f296
出典データセット
uspto-grants-2016_01
特許番号
US09238656B2

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