Sodium Iodide → N-({4-[4-(4-pyrrolidin-1-ylbutoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)pyridin-2-amine

HRID 273039ノート

反応式

HRID 273039 の反応式
Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2([CH2:19][NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:9][CH:8]=1.[NH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+]>C(O)CCC>[N:27]1([CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3([CH2:19][NH:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=4)[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[CH:9][CH:8]=2)[CH2:31][CH2:30][CH2:29][CH2:28]1

参加物

6

反応物 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 31268PyrrolidineHCID 68576502N-({4-[4-(4-chlorobutoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)pyridin-2-amine

生成物 1

HCID 59837489N-({4-[4-(4-pyrrolidin-1-ylbutoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)pyridin-2-amine収率 29%

試薬・触媒・溶媒 1

HCID 2631-Butanol溶媒

実験手順

A mixture of N-({4-[4-(4-chlorobutoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)pyridin-2-amine (180 mg, 0.481 mmol), pyrrolidine (80 μl, 0.963 mmol), sodium carbonate (102 mg, 0.963 mmol) and sodium iodide (4 mg, 0.024 mmol) were stirred in butanol (5 ml) at 100° C. for 24 hours until complete. Butanol was removed in vacuo and the residue partitioned between ethyl acetate (40 ml) and water (40 ml). Organic layer was dried over sodium sulphate, filtered and concentrated in vacuo to give a brown solid. Solid was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (98:2:02 to 96:4:0.4 by volume), followed by recrystallisation from ether (1.5 ml) to give the title compound (56.6 mg, 29%). 1H NMR (400 MHz, CDCl3) δ 1.78-2.00 (m, 12H), 2.08-2.20 (m, 2H), 2.54-2.90 (m, 4H), 3.50 (d, 2H), 2.54-2.63 (m, 2H), 3.79-3.88 (m, 2H), 3.96-4.08 (m, 2H), 6.23 (d, 1H), 6.50 (t, 1H), 6.90 (d, 2H), 7.25 (d, 2H), 7.32 (t, 1H), 8.01 (d, 1H). LRMS APCI+ m/z 410 [MH]+.

後処理

  1. customButanol was removed in vacuo
  2. customthe residue partitioned between ethyl acetate (40 ml) and water (40 ml)
  3. dry with materialOrganic layer was dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a brown solid
  7. customSolid was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (98:2:02 to 96:4:0.4 by volume)
  8. customfollowed by recrystallisation from ether (1.5 ml)

出典と根拠

ORDレコード
ord-037c6caaf1da4a208977c10089a452e0
出典データセット
uspto-grants-2008_11
特許番号
US07456164B2

反応ノート

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