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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
ノート
印刷プレビュー

反応式

HRID 1473332 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 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

生成物 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-trifluoroacetate収率 182.3%

試薬・触媒・溶媒 1

HCID 887
Methanol
溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-672f0209cf4440cb951dad2317cd7836
出典データセット
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09012443B2

反応ノート

読み込み中…

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