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

HRID 449922노트

반응식

HRID 449922 반응식
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]

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 4311764Sodium borohydrideHCID 86648961HCID 86648961, 화합물

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매HCID 8857Ethyl Acetate용매

실험 절차

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+].

후처리

  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)

출처 및 근거

ORD 기록
ord-4310987ddc8d4a4daebf0e87d8b4fd5a
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486950B2

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