Triethylamine → 7-cyclopentyl-2-[5-((3aR,8aS)-octahydro-pyrrolo[2,3-c]azepine-7-carbonyl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide

HRID 627351ノート

反応式

HRID 627351 の反応式
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[C:25](=[O:29])[N:26]([CH3:28])[CH3:27])[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.C(OC([N:71]1[C@@H:75]2[CH2:76][NH:77][CH2:78][CH2:79][CH2:80][C@@H:74]2[CH2:73][CH2:72]1)=O)C1C=CC=CC=1>CN(C=O)C.C(OCC)(=O)C.[Pd].CO>[CH3:28][N:26]([CH3:27])[C:25]([C:7]1[N:6]([CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[C:10]2[N:11]=[C:12]([NH:15][C:16]3[CH:24]=[CH:23][C:19]([C:20]([N:77]4[CH2:78][CH2:79][CH2:80][C@@H:74]5[CH2:73][CH2:72][NH:71][C@@H:75]5[CH2:76]4)=[O:21])=[CH:18][N:17]=3)[N:13]=[CH:14][C:9]=2[CH:8]=1)=[O:29]

参加物

9

反応物 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 583154726-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinic acidHCID 67355838(3aR,8aS)-Octahydro-pyrrolo[2,3-c]azepine-1-carboxylic acid benzyl ester

生成物 1

HCID 673553587-cyclopentyl-2-[5-((3aR,8aS)-octahydro-pyrrolo[2,3-c]azepine-7-carbonyl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide

試薬・触媒・溶媒 4

HCID 23938Palladium触媒HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
23 °C

実験手順

A solution of 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino) nicotinic acid (5 eq of Lithium Chloride) (0.088 g, 0.146 mmol), HBTU (0.086 mg, 0.226 mmol, 1.6 eq) and triethylamine (0.100 mL, 0.717 mmol, 4.9 eq) in DMF (3 mL) was stirred at 23° C. for 5 minutes, then (3aR,8aS)-Octahydro-pyrrolo[2,3-c]azepine-1-carboxylic acid benzyl ester (0.040 mg, 0.146 mmol, 1.0 eq) was added and the reaction stirred at 23° C. for 1.5 hr. The reaction mixture was diluted with Ethyl Acetate, the mixture washed with 0.5M HCl (aq), then water (3×), brine, the organic layer dried (Na2SO4), filtered, and the filtrate concentrated. The crude was purified using chromatography (Methanol/CH2Cl2) giving a white solid. To the resulting solid (42 mg) was added 10% Pd/C (15 mg) followed by methanol (5 mL). The suspension was blanketed with H2 balloon with stirring for 6 hr. The contents of the reaction were filtered through Celite and the filtrate concentrated to a white solid that was burified by trituration from Ethyl Acetate/Heptane followed by chromatography (methanol/CH2Cl2) mixtures gave 7-cyclopentyl-2-[5-((3aR,8aS)-octahydro-pyrrolo[2,3-c]azepine-7-carbonyl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. (20 mg, 0.039 mmol, 27%). 1H NMR (400 MHz, MeOD) δ ppm 1.62-1.84 (m, 5H) 1.84-1.99 (m, 2H) 1.99-2.20 (m, 4H) 2.31 (dd, J=13.05, 5.02 Hz, 1H) 2.47-2.62 (m, 2H) 2.63-2.80 (m, 1H) 3.18-3.27 (m, 1H) 3.38-3.61 (m, 2H) 3.77 (d, J=13.05 Hz, 1H) 3.84-3.98 (m, 1H) 4.04 (t, J=7.53 Hz, 1H) 4.06-4.19 (m, 1H) 4.80 (quin, J=9.03, 8.87 Hz, 1H) 6.67 (s, 1H) 7.93 (dd, J=8.78, 2.26 Hz, 1H) 8.45 (d, J=2.01 Hz, 1H) 8.53 (d, J=8.53 Hz, 1H) 8.82 (s, 1H); HRMS calc for m/z=517.3039 and found m/z=517.3044 (M+H)+.

後処理

  1. washthe mixture washed with 0.5M HCl (aq)
  2. dry with materialwater (3×), brine, the organic layer dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated
  5. customThe crude was purified
  6. customgiving a white solid
  7. stirringwith stirring for 6 hr
  8. filtrationThe contents of the reaction were filtered through Celite
  9. concentrationthe filtrate concentrated to a white solid

出典と根拠

ORDレコード
ord-0df8d7f527fe45a1979b808a305269ae
出典データセット
uspto-grants-2016_04
特許番号
US09309252B2

反応ノート

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