Dichloromethane → (5-Aminomethyl-2-{[(5-chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-phenyl)-methanol

HRID 251263ノート

反応式

HRID 251263 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:30])[C:5]([CH2:8][N:9]([CH2:19][C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][C:21]=2[CH2:28][OH:29])[C:10]([CH3:18])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[CH3:11])=[N:6][CH:7]=1.[Li+].[BH4-].[OH-].[Na+].C(Cl)Cl>C1COCC1>[NH2:25][CH2:24][C:23]1[CH:26]=[CH:27][C:20]([CH2:19][N:9]([CH2:8][C:5]2[C:4]([CH3:30])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=2)[C:10]([CH3:18])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[CH3:11])=[C:21]([CH2:28][OH:29])[CH:22]=1

参加物

6

反応物 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 4148881Lithium borohydrideHCID 589971284-{[(5-Chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-3-hydroxymethyl-benzonitrile

生成物 1

HCID 58997153(5-Aminomethyl-2-{[(5-chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-phenyl)-methanol収率 48%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
70 °C

実験手順

To a solution of 4-{[(5-chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-3-hydroxymethyl-benzonitrile (0.5371 g, 1.2 mmol) in THF (12 mL) at 0° C. was added LiBH4 (0.2086 g, 9.6 mmol), then heated to 70° C. and stirred for 18 hours. 1N NaOH (25 mL) and CH2Cl2 (50 mL) were added and stirred for 10 minutes. The phases were separated and the aqueous phase was extracted with CH2Cl2 (3×50 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification of the crude material by column chromatography on silica gel (75:1:1 CH2Cl2-MeOH—NH4OH) provided 0.2330 g (48%) of COMPOUND 402 as a white solid. 1H NMR (CDCl3) δ 1.61 (s, 5H), 2.07 (s, 6H), 3.69 (s, 2H), 3.73 (s, 2H), 3.91 (s, 2H), 4.55 (s, 2H), 6.69-6.78 (bs, 1H), 6.94-6.97 (m, 1H), 7.02-7.08 (m, 3H), 7.21 (d, 1H, J=1.5 Hz), 7.49-7.55 (m, 1H), 7.77 (d, 1H, J=8.1 Hz), 8.05 (d, 1H, J=2.1 Hz), 8.45-8.48 (m, 1H). 13C NMR (CDCl3) δ 18.71, 24.43, 46.39, 51.43, 53.95, 63.49, 64.78, 122.10, 123.09, 126.25, 129.32, 130.26, 131.30, 132.25, 136.21, 137.16, 137.26, 141.33, 143.29, 144.59, 147.94, 156.80, 165.90. ES-MS m/z 425.4 (M+H). Anal. Calcd. for C24H29N4ClO.0.3H2O: C, 66.98; H, 6.93; N, 13.02; Cl, 8.24. Found: C, 67.11; H, 6.54; N, 12.13; Cl, 8.99.

後処理

  1. stirringstirred for 10 minutes
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with CH2Cl2 (3×50 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography on silica gel (75:1:1 CH2Cl2-MeOH—NH4OH)

出典と根拠

ORDレコード
ord-01291c2901754d7b82a833911d56cc62
出典データセット
uspto-grants-2011_01
特許番号
US07863293B2

反応ノート

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