Sodium Hydroxide → 5-(4-((6-(7-(4-(3-Cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)piperazin-1-yl)pentanoic acid

HRID 1400951Notes

Reaction equation

HRID 1400951 reaction equation
[CH:1]1([NH:4][C:5](=[O:46])[NH:6][C:7]2[CH:44]=[CH:43][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:26]=[CH:25][C:24]([CH2:27][N:28]6[CH2:33][CH2:32][N:31]([CH2:34][CH2:35][CH2:36][CH2:37][C:38]([O:40]CC)=[O:39])[CH2:30][CH2:29]6)=[CH:23][CH:22]=5)[S:20][C:13]=34)=[C:9]([F:45])[CH:8]=2)[CH2:3][CH2:2]1.[OH-].[Na+]>CO.C1COCC1>[CH:1]1([NH:4][C:5](=[O:46])[NH:6][C:7]2[CH:44]=[CH:43][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:26]=[CH:25][C:24]([CH2:27][N:28]6[CH2:29][CH2:30][N:31]([CH2:34][CH2:35][CH2:36][CH2:37][C:38]([OH:40])=[O:39])[CH2:32][CH2:33]6)=[CH:23][CH:22]=5)[S:20][C:13]=34)=[C:9]([F:45])[CH:8]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67443956Ethyl 5-(4-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)piperazin-1-yl)pentanoate

Product 1

HCID 674409705-(4-((6-(7-(4-(3-Cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)piperazin-1-yl)pentanoic acidYield 73.8%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 517 (94 mg, 0.145 mmol) in a mixture of MeOH/THF (5/5 mL) was added 1N NaOH (1.45 mL). The reaction mixture was heated at 60° C. for 1.5 h, then at rt. The reaction mixture was concentrated, diluted with water, neutralyzed with 1N HCl (pH around 5-6) until precipitation occurred. The suspension was shaken for 15 min and the gel was collected by filtration, rinsed with water, and dried under high vacuum to afford the desired product 518 (66 mg, 0.107 mmol, 73% yield) as a white fluffy solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): the carboxylic OH is missing, 8.78 (s, 1H), 8.56 (bd, J=1.4 Hz, 1H), 8.52 (d, J=5.5 Hz, 1H), 8.33 (s, 1H), 8.25 (d, J=8.0 Hz, 1H), 7.86 (dd, J=8.2, 2.0 Hz, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.1 Hz, 1H), 7.20 (dd, J=8.9, 1.3 Hz, 1H), 6.65 (dd, J=5.4, 0.7 Hz, 1H), 6.60 (bd, J=2.5 Hz, 1H), 3.58 (s, 2H), 2.70-2.30 (m, 11H), 2.26-2.18 (m, 2H), 1.56-1.40 (m, 4H), 0.72-0.58 (m, 2H), 0.49-0.36 (m, 2H). MS (m/z): 619.5 (M+H).

Workup

  1. customat rt
  2. concentrationThe reaction mixture was concentrated
  3. additiondiluted with water
  4. customneutralyzed with 1N HCl (pH around 5-6) until precipitation
  5. filtrationthe gel was collected by filtration
  6. washrinsed with water
  7. customdried under high vacuum

Sources & evidence

ORD record
ord-b5fa070e894044e58b89ba3065ef8770
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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