Triethylamine → 2,6-dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)-4-((dimethylamino)methyl)benzamide

HRID 449922ノート

反応式

HRID 449922 の反応式
C[CH2:2][N:3](CC)[CH2:4]C.N(C)C.Cl.[Cl:12][C:13]1[CH:33]=[C:32]([CH:34]=O)[CH:31]=[C:30]([Cl:36])[C:14]=1[C:15]([NH:17][C:18]1[CH:23]=[CH:22][N:21]=[C:20]([NH:24][C:25]([CH:27]2[CH2:29][CH2:28]2)=[O:26])[CH:19]=1)=[O:16].[BH4-].[Na+]>CO.CCOC(C)=O>[Cl:36][C:30]1[CH:31]=[C:32]([CH2:34][N:3]([CH3:4])[CH3:2])[CH:33]=[C:13]([Cl:12])[C:14]=1[C:15]([NH:17][C:18]1[CH:23]=[CH:22][N:21]=[C:20]([NH:24][C:25]([CH:27]2[CH2:29][CH2:28]2)=[O:26])[CH:19]=1)=[O:16]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 4311764Sodium borohydrideHCID 86648961HCID 86648961、化合物

生成物 1

HCID 596183342,6-dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)-4-((dimethylamino)methyl)benzamide収率 36.8%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of Et3N (121 mg, 1.2 mmol) in absolute methanol (1 mL) was added Me2NH HCl (103 mg, 1.2 mmol), Ti(O-iPr)4 (114 mg, 0.40 mmol), and 2,6-dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)-4-formylbenzamide (80 mg, 0.20 mmol). The reaction was stirred at room temperature for 9 hours and then NaBH4 (12 mg, 0.30 mmol) was added. The resulting mixture was stirred for 10 hours and then diluted with EtOAc (20 mL). The organic solution was washed with water (3×10 ml) and then concentrated under reduced pressure. The residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to afford the desired product (30 mg, 31% yield). 1H NMR (500 MHz, MeOH-d4): δ 8.31 (s, 1H), 8.24 (s, 1H), 7.60 (m, 1H), 7.48 (s, 2H), 3.52 (s, 2H), 2.28 (s, 6H), 1.91 (m, 1H), 1.02-0.98 (m, 2H), 0.94-0.90 (m, 2H). LCMS (ESI) m/z: 407.1 [M+H+].

後処理

  1. stirringThe resulting mixture was stirred for 10 hours
  2. washThe organic solution was washed with water (3×10 ml)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

出典と根拠

ORDレコード
ord-4310987ddc8d4a4daebf0e87d8b4fd5a
出典データセット
uspto-grants-2013_07
特許番号
US08486950B2

反応ノート

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