Methanol → 4-(8-{4-[2-(4-Hydroxy-piperidin-1-yl)-thiazol-4-ylmethyl]-[1,4]diazepan-1-yl}-6-methyl-quinolin-7-yloxy)-butyric acid

HRID 2063577Notes

Reaction equation

HRID 2063577 reaction equation
C[O:2][C:3](=[O:39])[CH2:4][CH2:5][CH2:6][O:7][C:8]1[C:17]([N:18]2[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][C:26]3[N:27]=[C:28]([N:31]4[CH2:36][CH2:35][CH:34]([OH:37])[CH2:33][CH2:32]4)[S:29][CH:30]=3)[CH2:20][CH2:19]2)=[C:16]2[C:11]([CH:12]=[CH:13][CH:14]=[N:15]2)=[CH:10][C:9]=1[CH3:38].[OH-].[Na+].CO>C1COCC1>[OH:37][CH:34]1[CH2:33][CH2:32][N:31]([C:28]2[S:29][CH:30]=[C:26]([CH2:25][N:21]3[CH2:22][CH2:23][CH2:24][N:18]([C:17]4[C:8]([O:7][CH2:6][CH2:5][CH2:4][C:3]([OH:39])=[O:2])=[C:9]([CH3:38])[CH:10]=[C:11]5[C:16]=4[N:15]=[CH:14][CH:13]=[CH:12]5)[CH2:19][CH2:20]3)[N:27]=2)[CH2:36][CH2:35]1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 593661684-(8-{4-[2-(4-Hydroxy-piperidin-1-yl)-thiazol-4-ylmethyl]-[1,4]diazepan-1-yl}-6-methyl-quinolin-7-yloxy)-butyric acid methyl ester

Product 1

HCID 462034114-(8-{4-[2-(4-Hydroxy-piperidin-1-yl)-thiazol-4-ylmethyl]-[1,4]diazepan-1-yl}-6-methyl-quinolin-7-yloxy)-butyric acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The product from step 3 (3.27 mmol) was dissolved in THF (10.9 mL), and 1 N aq. NaOH (6.54 mL, 6.54 mmol) was added, followed by MeOH (5.5 mL). This solution was allowed to stir for 3 h, then concentrated. The crude product was then purified on a reverse phase column (MeCN:H2O+0.1% TFA), and the combined product fractions were basified to pH 9 using NH4OH, then extracted with CH2Cl2 (3×50 mL). The combined organic was then concentrated. The residue was lyophilized from MeCN/H2O to give the product as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.70 (dd, 1H, J=1.4, 4.2 Hz), 7.96 (dd, 1H, J=1.4, 8.2 Hz), 7.35 (s, 1H), 7.22 (dd, 1H, J=4.4, 8.0 Hz), 6.71 (s, 1H), 4.12-4.05 (m, 4H), 4.05-3.82 (m, 4H), 3.80-3.72 (m, 4H), 3.62-3.56 (m, 2H), 3.49-3.40 (m, 4H), 3.22-3.15 (m, 2H), 2.58 (t, 2H, J=7.0 Hz), 2.41 (s, 3H), 2.24-2.17 (m, 4H), 1.98-1.90 (m, 2H), 1.69-1.59 (m, 2H). MS (ES) m/z 540.5 (M+H+).

Workup

  1. concentrationconcentrated
  2. customThe crude product was then purified on a reverse phase column (MeCN:H2O+0.1% TFA)
  3. extractionextracted with CH2Cl2 (3×50 mL)
  4. concentrationThe combined organic was then concentrated

Sources & evidence

ORD record
ord-b4819cfe64d24092abbeabfc9c46612a
Source dataset
uspto-grants-2012_10
Patent number
US08288373B2

Reaction notes

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