Acetic Acid → HCID 59226969, 화합물

HRID 888458노트

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HRID 888458 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[C:29]#[N:30])[C:5]([NH:7][C:8]1[C:13]([CH3:14])=[CH:12][C:11]([C:15]([F:24])([C:20]([F:23])([F:22])[F:21])[C:16]([F:19])([F:18])[F:17])=[CH:10][C:9]=1[CH3:25])=[O:6].C=O.[C:33](O)(=O)C.[BH4-].[Na+]>C(#N)C>[C:29]([C:28]1[CH:27]=[CH:26][C:4]([C:5]([NH:7][C:8]2[C:13]([CH3:14])=[CH:12][C:11]([C:15]([F:24])([C:20]([F:21])([F:22])[F:23])[C:16]([F:17])([F:18])[F:19])=[CH:10][C:9]=2[CH3:25])=[O:6])=[CH:3][C:2]=1[NH:1][CH3:33])#[N:30]

참가 물질

6

반응물 4

HCID 176Acetic Acid2회HCID 712FormaldehydeHCID 4311764Sodium borohydrideHCID 59226943HCID 59226943, 화합물

생성물 1

HCID 59226969HCID 59226969, 화합물수율 58%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

3-Amino-4-cyano-N[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-benzamide (3.01 g, 6.95 mmol) (Example I2) was dissolved in acetonitrile (50 ml) and aqueous formaldehyde (36.5% w/v) (0.64 ml, 6.95 mmol) and acetic acid (30 ml) were added successively. The reaction mixture was stirred at ambient temperature for 45 minutes. Then sodium borohydride (0.44 g, 6.95 mmol) and more acetic acid (5 ml) were added. The reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was concentrated. The residue was dissolved in ethyl acetate and the solution washed with aqueous sodium hydroxide (1N). The aqueous phase was extracted three times with ethyl acetate (200 ml). The combined organic extracts were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1:5) to give 4-cyano-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-3-methylamino-benzamide (1.80 g, 58% yield). M.p. 204-206° C. 1H-NMR (400 MHz, CDCl3): 7.53 (d, 1H), 7.37 (s, 3H), 7.23 (s, 1H), 7.10 (q, 1H), 5.88 (d, 1H), 3.02 (d, 3H), 2.35 (s, 6H) ppm. The method as described in Example P1 was then used to prepare Compound No. A3 of Table A.

후처리

  1. stirringThe reaction mixture was stirred at ambient temperature for 2 hours
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washthe solution washed with aqueous sodium hydroxide (1N)
  5. extractionThe aqueous phase was extracted three times with ethyl acetate (200 ml)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1:5)

출처 및 근거

ORD 기록
ord-e18b5226406c4885801829f931100f9e
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08247594B2

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