Sodium Bicarbonate → {4-[2-(4-trifluoromethylphenyl)-pyrimidin-4-yl]-phenyl}-carbamic acid (2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester

HRID 1470826ノート

反応式

HRID 1470826 の反応式
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=3)[CH:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.C[Si](C)(C)[N-][Si](C)(C)C.[K+].[CH3:34][O:35][CH:36]1[CH:41]([O:42][CH3:43])[CH:40]([O:44][CH3:45])[CH:39]([CH3:46])[O:38][CH:37]1[O:47][C:48](=O)[O:49]C1C=CC([N+]([O-])=O)=CC=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[CH3:34][O:35][C@@H:36]1[C@H:41]([O:42][CH3:43])[C@@H:40]([O:44][CH3:45])[C@H:39]([CH3:46])[O:38][C@H:37]1[O:47][C:48](=[O:49])[NH:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]2[CH:12]=[CH:11][N:10]=[C:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:22])[F:23])=[CH:8][CH:7]=3)[N:14]=2)=[CH:16][CH:17]=1

参加物

6

反応物 4

HCID 516892Sodium BicarbonateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 669688834-[2-(4-Trifluoromethylphenyl)-pyrimidin-4-yl]-phenylamineHCID 67519234Carbonic acid 4-nitrophenyl ester 3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester

生成物 1

HCID 44230217{4-[2-(4-trifluoromethylphenyl)-pyrimidin-4-yl]-phenyl}-carbamic acid (2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester収率 29.2%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒3 回

実験手順

To a mixture cooled in an ice bath of 126 mg (0.40 mmol) of 4-[2-(4-trifluoromethylphenyl)-pyrimidin-4-yl]-phenylamine in 1 mL of dry toluene was added dropwise via syringe 1.6 mL (0.80 mmol) of a 0.5 M solution of potassium hexamethyldisilazide in toluene over a 10-15 minute period. To this mixture was then added dropwise a solution of 148 mg (0.400 mmol) of carbonic acid 4-nitrophenyl ester 3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester in 2 mL of toluene. The contents were allowed to gradually warm to room temperature and stir overnight and were added to cold saturated sodium bicarbonate. The mixture was extracted two times with chloroform and the combined extracts were dried (MgSO4). Concentration gave 130 mg which was purified by chromatography on silica gel using 9:1 DCM/EtOAc to afford 64 mg (29%) of Compound 232. 1HNMR (300 MHz, CDCl3) δ 8.87 (d, J=5.2 Hz, 1H), 8.71 (d, J=8.2 Hz, 2H), 8.26 (d, J=8.8 Hz, 2H), 7.79 (d, J=8.2 Hz, 2H), 7.65 (d, J=5.2 Hz, 1H), 7.63 (d, 2H), 6.86 (br s, 1H), 6.26 (d, J=1.9 Hz, 1H), 3.74-3.70 (m, 2H), 3.61 (s, 3H), 3.60 (s, 3H), 3.57 (s, 3H), 3.53 (m, 1H), 3.24 (t, J=9.5 Hz, 1H), 1.36 (d, J=6.0 Hz, 3H); MS (API-ES+) 549 ([M+H]+, 10), 358 (100); mp 176-179° C.

後処理

  1. extractionThe mixture was extracted two times with chloroform
  2. dry with materialthe combined extracts were dried (MgSO4)
  3. concentrationConcentration
  4. customgave 130 mg which
  5. customwas purified by chromatography on silica gel using 9:1 DCM/EtOAc

出典と根拠

ORDレコード
ord-a0ba20dc408f4aa08d1e871d0d744d2b
出典データセット
uspto-grants-2015_04
特許番号
US09006468B2

反応ノート

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