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 1400809Notes

Reaction equation

HRID 1400809 reaction equation
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

Participants

4

Reactant 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

Product 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)acetamideYield 72%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-04e23dc3534f4704b4e4393d93a26909
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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