Trifluoroacetic acid methylene chloride → HCID 178488236、化合物

HRID 432490

反応式

HRID 432490 の反応式
FC(F)(F)C(O)=O.ClCCl.[NH2:11][C:12]1[N:17]=[CH:16][N:15]=[C:14]2[N:18]([C@H:38]3[CH2:43][CH2:42][C@H:41]([N:44]4[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]4)[CH2:40][CH2:39]3)[N:19]=[C:20]([C:21]3[C:26]([F:27])=[CH:25][C:24]([NH:28]C(=O)OC(C)(C)C)=[C:23]([O:36][CH3:37])[CH:22]=3)[C:13]=12>ClCCl>[NH2:28][C:24]1[C:23]([O:36][CH3:37])=[CH:22][C:21]([C:20]2[C:13]3[C:14](=[N:15][CH:16]=[N:17][C:12]=3[NH2:11])[N:18]([C@H:38]3[CH2:43][CH2:42][C@H:41]([N:44]4[CH2:45][CH2:46][N:47]([CH3:50])[CH2:48][CH2:49]4)[CH2:40][CH2:39]3)[N:19]=2)=[C:26]([F:27])[CH:25]=1

参加物

4

反応物 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 178488238HCID 178488238、化合物

生成物 1

HCID 178488236HCID 178488236、化合物収率 87.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of trifluoroacetic acid/dichloromethane (20:80, 7 mL) was added to a solution of trans-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-5-fluoro-2-methoxyphenyl)carbamate (250 mg, 0.451 mmol) in dichloromethane (4.0 mL) at 0° C. After 15 minutes, the ice-bath was removed and the reaction mixture was stirred at room temperature for 4 hours. Solvent was then evaporated and the residue was dissolved in dichloromethane. Saturated sodium bicarbonate was added to adjust the pH to 8. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with brine, dried over MgSO4, filtered and evaporated give trans-3-(4-amino-2-fluoro-5-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (179 mg, 87%). 1H NMR (CDCl3) δ 1.56 (m, 2H), 2.15 (m, 7H), 2.31 (s, 3H), 2.51 (m, 4H), 2.67 (m, 4H), 3.88 (s, 3H), 4.16 (bs, 2H), 4.74 (m, 1H), 5.64 (bs, 2H), 6.56 (d, J=10.84 Hz, 1H), 6.88 (d, J=6.55 Hz, 1H), 8.33 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+ =455.2, Rt=0.63 min.

後処理

  1. customthe ice-bath was removed
  2. customSolvent was then evaporated
  3. dissolutionthe residue was dissolved in dichloromethane
  4. additionSaturated sodium bicarbonate was added
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with dichloromethane
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated

出典と根拠

ORDレコード
ord-adda46c6dd314e4f89860bb0bad3fe53
出典データセット
uspto-grants-2003_12
特許番号
US06660744B1

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