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Formaldehyde → 5-(2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)naphthalene-2-sulfonamide 2,2,2-trifluoroacetate

HRID 1473332
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HRID 1473332 반응식
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[N:8]1[CH:13]=[CH:12][C:11]([NH:14][S:15]([C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][C:24]=3[C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][C:29]=3[C:38]3[CH2:39][CH2:40][NH:41][CH2:42][CH:43]=3)[CH:19]=2)(=[O:17])=[O:16])=[N:10][CH:9]=1.C=O.[Na]>CO>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:2][N:41]1[CH2:40][CH:39]=[C:38]([C:29]2[CH:30]=[C:31]([C:34]([F:35])([F:36])[F:37])[CH:32]=[CH:33][C:28]=2[C:24]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:25]=2[CH:26]=[CH:27][C:18]([S:15]([NH:14][C:11]2[CH:12]=[CH:13][N:8]=[CH:9][N:10]=2)(=[O:17])=[O:16])=[CH:19]3)[CH2:43][CH2:42]1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 712FormaldehydeHCID 5360545SodiumHCID 86687370N-(pyrimidin-4-yl)-5-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)naphthalene-2-sulfonamide 2,2,2-trifluoroacetate

생성물 1

HCID 866873855-(2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)naphthalene-2-sulfonamide 2,2,2-trifluoroacetate수율 182.3%

시약·촉매·용매 1

HCID 887
Methanol
용매

실험 절차

To a round bottom flask charged with N-(pyrimidin-4-yl)-5-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)naphthalene-2-sulfonamide (EXAMPLE 48, 167.0 mg, 0.327 mmol) was added MeOH (3271 μl), then formaldehyde (265 μl, 3.27 mmol). The solution was maintained at rt for 15 min, then sodium triacetoxyhydroborate (693 mg, 3.27 mmol) was added portionwise. After 10 min, the reaction mixture was partitioned between ice and saturated NaHCO3 and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (1×25 mL). The combined organic extracts were washed with brine (1×20 mL) and dried over Na2SO4 and concentrated under a vacuum. The residue was taken up in minimal MeOH and purified by reverse phase preparative HPLC (20 to 80% CH3CN:H2O (1% TFA modifier) over 15 min). Clean fractions were combined and concentrated to afford 5-(2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)naphthalene-2-sulfonamide 2,2,2-trifluoroacetate (190 mg, 0.298 mmol) as a off-white amorphous solid. 1H NMR (400 MHz, MeOH) δ ppm 1.98-2.47 (m, 2H) 2.49-2.90 (m, 4H) 3.08-3.28 (m, 1H) 3.37-3.58 (m, 1H) 3.64-3.90 (m, 1H) 5.68 (d, J=8.51 Hz, 1H) 7.16 (dd, J=6.36, 0.98 Hz, 1H) 7.54 (d, J=8.02 Hz, 1H) 7.58-7.69 (m, 2H) 7.70-7.85 (m, 3H) 7.94 (d, J=8.61 Hz, 1H) 8.18 (d, J=8.31 Hz, 1H) 8.30 (d, J=6.36 Hz, 1H) 8.60 (s, 1H) 8.72 (d, J=1.37 Hz, 1H); m/z (ESI, +ve ion) 525.2 (M+H)+.

후처리

  1. customthe reaction mixture was partitioned between ice and saturated NaHCO3 and EtOAc
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (1×25 mL)
  4. washThe combined organic extracts were washed with brine (1×20 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under a vacuum
  7. custompurified by reverse phase preparative HPLC (20 to 80% CH3CN:H2O (1% TFA modifier) over 15 min)
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-672f0209cf4440cb951dad2317cd7836
출처 데이터셋
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09012443B2

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