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Hydrochloric Acid → Lcq908

HRID 76056
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HRID 76056 반응식
C[O:2][C:3](=[O:34])[CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24]4[CH:25]=[N:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=4)=[CH:19][N:18]=3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.[Li+].[OH-].Cl>C1COCC1>[F:33][C:30]([F:31])([F:32])[C:27]1[N:26]=[CH:25][C:24]([NH:23][C:20]2[CH:21]=[CH:22][C:17]([C:14]3[CH:15]=[CH:16][C:11]([CH:8]4[CH2:7][CH2:6][CH:5]([CH2:4][C:3]([OH:34])=[O:2])[CH2:10][CH2:9]4)=[CH:12][CH:13]=3)=[N:18][CH:19]=2)=[CH:29][CH:28]=1
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참가 물질

5

반응물 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 24938267Methyl 2-((1r,4r)-4-(4-(5-((6-(trifluoromethyl)pyridin-3-yl)amino)pyridin-2-yl)phenyl)cyclohexyl)acetate

생성물 1

HCID 53387035Lcq908

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
50 °C

실험 절차

A THF solution of (4-{4-[5-(6-trifluoromethyl-pyridin-3-ylamino)-pyridin-2-yl]-phenyl}-cyclohexyl)-acetic acid methyl ester was treated with 10% aqueous LiOH and heated to 50° C. overnight. Upon reaction completion, the mixture was acidified with concentrated HCl. The resulting precipitate was isolated by filtration to afford the title compound: 1H NMR (400 MHz, DMSO-d6) δ 1.08-1.19 (m, 1H) 1.14 (dd, J=12.63, 2.27 Hz, 1H) 1.44-1.56 (m, 1H) 1.50 (dd, J=12.51, 2.65 Hz, 1H) 1.75 (br. S., 1H) 1.84 (d, J=10.61 Hz, 4H) 2.14 (d, J=6.82 Hz, 2H) 2.54 (m, 1H) 7.33 (d, J=8:34 Hz, 2H) 7.65 (d, J=2.53 Hz, 1H) 7.68-7.74 (m, 1H) 7.70 (d, J=8.34 Hz, 1H) 7.89 (d, J=8.59 Hz, 1H) 7.95 (d, J=8.59 Hz, 2H) 8.46 (d, J=2.78 Hz, 1H) 8.54 (d, J=2.53 Hz, 1H) 9.20 (s, 1H); (M+H)+456.3. Alternatively, the methyl ester can be dissolved in a mixture of THF and water, and treated with aqueous sodium hydroxide (4 equiv). The mixture can then be stirred at 50 degrees for 12 hours, at which point the THF is removed under reduced pressure to yield an opaque, white slurry, which affords the title compound as the corresponding sodium salt upon filtration. 1H NMR (DMSO-d6, 500 MHz) δ 10.05 (s, 1H), 8.59 (d, 1H, J=2.8 Hz), 8.54 (s, 1H), 7.92 (d, 2H, J=8.2 Hz), 7.86 (d, 1H, J=8.8 Hz), 7.75 (dd, 1H, J=8.7.2.7 Hz), 7.69 (s, 2H), 7.27 (d, 2H, J=8.5 Hz), 2.45 (m, 1H), 1.84 (m, 4H), 1.67-1.80 (m, 3H), 1.41 (m, 2H), 1.02 (m, 2H); MS m/z 456 (M-Na+2H)+.

후처리

  1. customUpon reaction completion
  2. customThe resulting precipitate was isolated by filtration

출처 및 근거

ORD 기록
ord-c975ada4302a4d3aab1808307125b0e4
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08835451B2

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