Sodium Carbonate → 4-Amino-2-morpholin-4-ylmethyl-thieno[3,2-c]pyridine-7-carboxylic acid amide

HRID 1268854ノート

反応式

HRID 1268854 の反応式
Br[C:2]1[CH:3]=[C:4]([CH2:7][N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[S:5][CH:6]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].[NH2:37][C:38]1C2C=C(Br)SC=2[C:41]([C:48]([NH2:50])=[O:49])=[CH:40][N:39]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:37][C:38]1[C:2]2[CH:3]=[C:4]([CH2:7][N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[S:5][C:6]=2[C:41]([C:48]([NH2:50])=[O:49])=[CH:40][N:39]=1

参加物

8

反応物 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 7834974-[(4-Bromothien-2-YL)methyl]morpholineHCID 2733548Bis(pinacolato)diboraneHCID 588407134-Amino-2-Bromothieno[3,2-C]pyridine-7-Carboxamide

生成物 1

HCID 690663124-Amino-2-morpholin-4-ylmethyl-thieno[3,2-c]pyridine-7-carboxylic acid amide収率 83.3%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒2 回HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

To a mixture of 4-(4-bromo-thiophen-2-ylmethyl)-morpholine 64 (173 mg, 0.66 mmol), bis(pinacolato)diboron (352 mg, 1.39 mmol.), Pd(PPh3)4 (76 mg, 0.07 mmol) and KOAc (194 mg, 2.0 mmol) was added degassed DMF (5 mL). The reaction mixture was heated at 120° C. under N2 for 2 h and then cooled down to room temperature. A solution of 4-amino-2-bromo-thieno[3,2-c]pyridine-7-carboxylic acid amide 17 (150 mg, 0.55 mmol), Pd(PPh3)4 (69 mg, 0.06 mmol) and Na2CO3 (1.0 mL of a 2M aqueous solution, 3.3 mmol) in DMF (2.0 mL) was added. The resulting mixture was heated at 90° C. for 1.5 h. The solvent was then removed via vacuum, the residue was dissolved in DMSO (4.0 mL) and the mixture purified by reverse phase preparative HPLC to give 66 (134 mg). 1H NMR (400 MHz, CDCl3) δ, 3.12 (m, 2H), 3.32 (m, 2H), 3.82 (m, 2H), 3.95 (m, 2H), 4.62 (s, 2H), 7.75 (s, 1H), 7.81 (br, 1H), 8.09 (s, 1H), 8.34 (s, 1H), 8.38 (br, 1H), 8.56 (s, 1H), 9.19 (br, 1H), 11.73 (br, 1H). MS (EI) m/z (M+H+) 375.

後処理

  1. additionwas added
  2. customdegassed DMF (5 mL)
  3. temperaturecooled down to room temperature
  4. temperatureThe resulting mixture was heated at 90° C. for 1.5 h
  5. customThe solvent was then removed via vacuum
  6. dissolutionthe residue was dissolved in DMSO (4.0 mL)
  7. customthe mixture purified by reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-c3ea4ce15c0d4dfc99367f4112be5a05
出典データセット
uspto-grants-2007_04
特許番号
US07199119B2

反応ノート

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