Sodium Hydroxide → N-((6-(7-(6-(3-cyclopropylureido)pyridin-3-yloxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)-2-hydroxy-N-(2-methoxyethyl)acetamide

HRID 1400809ノート

反応式

HRID 1400809 の反応式
C([O:4][CH2:5][C:6]([N:8]([CH2:13][C:14]1[CH:15]=[N:16][C:17]([C:20]2[S:28][C:27]3[C:22](=[N:23][CH:24]=[CH:25][C:26]=3[O:29][C:30]3[CH:31]=[N:32][C:33]([NH:36][C:37]([NH:39][CH:40]4[CH2:42][CH2:41]4)=[O:38])=[CH:34][CH:35]=3)[CH:21]=2)=[CH:18][CH:19]=1)[CH2:9][CH2:10][O:11][CH3:12])=[O:7])(=O)C.[OH-].[Na+]>CO>[CH:40]1([NH:39][C:37](=[O:38])[NH:36][C:33]2[N:32]=[CH:31][C:30]([O:29][C:26]3[CH:25]=[CH:24][N:23]=[C:22]4[CH:21]=[C:20]([C:17]5[N:16]=[CH:15][C:14]([CH2:13][N:8]([CH2:9][CH2:10][O:11][CH3:12])[C:6](=[O:7])[CH2:5][OH:4])=[CH:19][CH:18]=5)[S:28][C:27]=34)=[CH:35][CH:34]=2)[CH2:41][CH2:42]1

参加物

4

反応物 2

HCID 14798Sodium HydroxideHCID 674421792-(((6-(7-(6-(3-Cyclopropylureido)pyridin-3-yloxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)amino)-2-oxoethyl acetate

生成物 1

HCID 67442923N-((6-(7-(6-(3-cyclopropylureido)pyridin-3-yloxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)-2-hydroxy-N-(2-methoxyethyl)acetamide収率 72%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a stirred solution of 30 (from the previous step) in MeOH/THE (15/5 mL) was added 1N NaOH (2.6 mL). The reaction mixture was stirred at RT overnight, concentrated and diluted with water. The resultant suspension was shaken for 15 min. The solid was collected by filtration, rinsed with water and air-dried. The residue was purified by Biotage (SiliaSep 25 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV) to produce a material that upon trituration with methanol afforded the title compound 31 (79 mg, 0.144 mmol, 72% over 2 steps) as a white fluffy solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): mixture of rotamers, 9.23 (bs, 1H), 8.56-8.49 (m, 2H), 8.38-8.20 (m, 3H), 7.84-7.70 (m, 3H), 7.66 (bd, J=9.0 Hz, 1H), 6.73-6.67 (m, 1H), 4.82-4.57 (m, 3H), 4.23 and 4.13 (2d, J=6.0 Hz, 2H), 3.52-3.39 (m, 4H), 3.23-3.21 (2s, 3H), 2.65-2.57 (m, 1H), 0.74-0.60 (m, 2H), 0.53-0.37 (m, 2H). MS (m/z): 549.6 (M+H).

後処理

  1. concentrationconcentrated
  2. additiondiluted with water
  3. stirringThe resultant suspension was shaken for 15 min
  4. filtrationThe solid was collected by filtration
  5. washrinsed with water
  6. customair-dried
  7. customThe residue was purified by Biotage (SiliaSep 25 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV)
  8. customto produce a material that upon trituration with methanol

出典と根拠

ORDレコード
ord-04e23dc3534f4704b4e4393d93a26909
出典データセット
uspto-grants-2014_12
特許番号
US08906852B2

反応ノート

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