Formaldehyde → HCID 21071654、化合物

HRID 1371928ノート

反応式

HRID 1371928 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:11][CH2:12][NH:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][CH:23]([F:25])[F:24])[CH:16]=3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C=O.[C:28](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:11][CH2:12][N:13]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][CH:23]([F:25])[F:24])[CH:16]=3)[CH3:28])=[CH:7][NH:8]2)=[CH:4][CH:3]=1

参加物

6

反応物 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 21071426HCID 21071426、化合物

生成物 1

HCID 21071654HCID 21071654、化合物

試薬・触媒・溶媒 2

HCID 887Methanol溶媒2 回HCID 63651,1-Dichloroethane溶媒

実験手順

Combine N-(2-(6-chloro-1H-indol-3-yl)ethyl)-3-(2,2-difluoroethoxy)benzylamine (276 mg, 0.76 mmol) and formaldehyde (55.5 μL of a 38% aqueous solution, 0.76 mmol) in dichloroethane (15 mL) and stir at room temperature for 10 minutes; then add in two portions over 10 minutes sodium triacetoxyborohydride (321 mg, 1.51 mmol). Stir the reaction mixture at room temperature overnight and dilute with methanol (10 mL) and quench with one drop of glacial acetic acid. Remove the solvent in vacuo, to give a residue, redissolve the crude residue in methanol and directly load onto a 10 g SCX column. After washing the column thoroughly with methanol, elute with 2N ammonia in methanol. Concentrate in vacuo to give the title compound as an oil. Dissolve the oil (239 mg, 0.64 mmol) in methanol (20 mL) and treat with a solution of ammonium chloride (36 mg, 0.67 mmol) in methanol (5 mL). Sonicate the mixture for 10 minutes before removal of the solvent in vacuo to give the title compound as the hydrochloride salt. Dissolve the salt in 10 mL of 1:1 acetonitrile-water and lyophilize overnight, providing a fluffy white solid. Triturate the solid with diethyl ether (10 mL) and acetonitrile (2 drops), filter, and dry to give the title compound as the hydrochloride salt: mp: 63.8–65.8° C.; 1H NMR (400 MHz, dmso-d6): 11.10 (br s, 1H), 7.52 (d, 1H, J=8.4 Hz) 7.36 (d, 1H, J=2.0 Hz), 7.40–7.26 (m, 2H), 7.22 (d, 1H, J=2.4 Hz), 7.20–7.11 (m, 1H), 7.04 (br d, 1H, J=7.6 Hz), 6.96 (dd, 1H, J=8.6, 1.4 Hz), 6.38 (tt, 1H, J=54.4, 3.6, Hz), 4.50–4.02 (br m, 2H), 4.30 (td, 2H, J=14.4, 3.2 Hz), 3.15 (br s, 4H), 2.68 (br s, 3H); MS (ES+): m/e 378.9 (M+1.

後処理

  1. customquench with one drop of glacial acetic acid
  2. customRemove the solvent in vacuo
  3. customto give a residue
  4. washAfter washing the column thoroughly with methanol
  5. washelute with 2N ammonia in methanol
  6. concentrationConcentrate in vacuo

出典と根拠

ORDレコード
ord-20a3dd32561e435d84d074ac57d5ab93
出典データセット
uspto-grants-2007_01
特許番号
US07157488B2

反応ノート

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