Water → ((1R,3R)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methyl dihydrogen phosphate

HRID 2199482ノート

反応式

HRID 2199482 の反応式
[NH2:1][C@:2]1([CH2:23][OH:24])[CH2:6][CH2:5][C@@H:4]([C:7]2[CH:16]=[CH:15][C:14]3[CH2:13][C@H:12]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH2:11][CH2:10][C:9]=3[CH:8]=2)[CH2:3]1.P(Cl)(Cl)([O:27][P:28](Cl)(Cl)=[O:29])=O.[OH2:34]>C(#N)C>[P:28]([OH:27])([OH:34])([O:24][CH2:23][C@@:2]1([NH2:1])[CH2:6][CH2:5][C@@H:4]([C:7]2[CH:16]=[CH:15][C:14]3[CH2:13][C@H:12]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH2:11][CH2:10][C:9]=3[CH:8]=2)[CH2:3]1)=[O:29]

参加物

5

反応物 3

HCID 962WaterHCID 4432411Diphosphoryl tetrachlorideHCID 78321972((1R,3R)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol

生成物 1

HCID 78321973((1R,3R)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methyl dihydrogen phosphate収率 13.68%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a stirred solution of ((1R,3R)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (Example 1, 10 mg, 0.030 mmol) in anhydrous acetonitrile (1 mL) at 0° C. was added pyrophosphoryl chloride (0.042 mL, 0.303 mmol). The clear solution obtained was stirred at the same temperature for 5 min and at RT overnight. After water (0.4 mL) was added, the mixture was stirred at RT for 1 h. Purification using reverse phase HPLC (Luna Axia 5μ c18 30×100 mm, 10 min. gradient from 40% to 100% of Solvent B, Solvent A: 0.1% TFA in water, Solvent B: 0.1% TFA in MeCN), concentration and lyophilization gave ((1R,3R)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methyl dihydrogen phosphate (2 mg, 4.15 μmol, 13.68% yield) as a white solid. HPLC retention time=3.94 min (Condition C); LC/MS M+1=410; 1H NMR (500 MHz, methanol-d4+KOH) δ 6.97-6.87 (m, 3H), 3.77-3.71 (m, 1H), 3.71-3.66 (m, 1H), 2.83-2.70 (m, 3H), 2.32 (dd, J=16.2, 10.7 Hz, 1H), 2.14-1.98 (m, 2H), 1.96-1.83 (m, 2H), 1.74-1.60 (m, 3H), 1.59-1.49 (m, 1H), 1.45-1.26 (m, 11H), 0.94-0.87 (m, 3H), one proton under methanol solvent peak (˜3.3 ppm).

後処理

  1. customThe clear solution obtained
  2. stirringthe mixture was stirred at RT for 1 h
  3. customPurification
  4. concentrationphase HPLC (Luna Axia 5μ c18 30×100 mm, 10 min. gradient from 40% to 100% of Solvent B, Solvent A: 0.1% TFA in water, Solvent B: 0.1% TFA in MeCN), concentration and lyophilization

出典と根拠

ORDレコード
ord-a7f140047310479394ed2439fba088b3
出典データセット
uspto-grants-2016_06
特許番号
US09359286B2

反応ノート

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