Hydrochloric Acid → HCID 72557675, compound

HRID 2220144Notes

Reaction equation

HRID 2220144 reaction equation
C([O:3][C:4](=[O:55])[CH:5]([O:7][P:8]([CH2:17][CH2:18][N:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32](=[O:54])[NH:33][C:34]3[CH:39]=[CH:38][C:37]([CH3:40])=[C:36]([NH:41][C:42]4[N:47]=[C:46]([C:48]5[CH:49]=[N:50][CH:51]=[CH:52][CH:53]=5)[CH:45]=[CH:44][N:43]=4)[CH:35]=3)=[CH:28][CH:27]=2)[CH2:21][CH2:20]1)([O:10]C1C=CC=CC=1)=[O:9])[CH3:6])C.[OH-].[Na+].Cl>C(#N)C.O>[OH:10][P:8]([CH2:17][CH2:18][N:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([C:32](=[O:54])[NH:33][C:34]3[CH:39]=[CH:38][C:37]([CH3:40])=[C:36]([NH:41][C:42]4[N:47]=[C:46]([C:48]5[CH:49]=[N:50][CH:51]=[CH:52][CH:53]=5)[CH:45]=[CH:44][N:43]=4)[CH:35]=3)=[CH:30][CH:31]=2)[CH2:21][CH2:20]1)([O:7][CH:5]([CH3:6])[C:4]([OH:55])=[O:3])=[O:9]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 725576762-{[2-(4-{4-[4-Methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenylcarbamoyl]-benzyl}-piperazin-1-yl)-ethyl]-phenoxy-phosphinoyloxy}-propionic acid ethyl ester

Product 1

HCID 72557675HCID 72557675, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To a solution of 2-{[2-(4-{4-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenylcarbamoyl]-benzyl}-piperazin-1-yl)-ethyl]-phenoxy-phosphinoyloxy}-propionic acid ethyl ester (6 mg, 0.008 mmol) in 2:1 acetonitrile/water (0.3 mL) was added 1N NaOH (50 μL, 0.048 mmol). The solution was allowed to stir at room temperature for 1 hour when completion of the reaction was observed by LCMS. The reaction was acidified by 1N HCl (50 μL) solution and purified by RP HPLC using a C18 column with a gradient of H2O— Acetonitrile (5-100%) over 20 minutes to provide 2 mg (38%) of the product. 1H NMR (300 MHz, CD3OD) δ 1.51 (d, 3H, J=7 Hz), 2.04 (m, 2H), 2.33 (s, 3H), 2.96 (bs, 4H), 3.31 (m, 2H), 3.4 (bs, 4H), 3.89 (s, 2H), 4.88 (1H, possible overlap with solvent), 7.30 (m, 2H), 7.48-7.57 (m, 4H), 7.96-7.99 (m, 4H), 8.32 (s, 1H), 8.56 (d, 1H, J=5 Hz), 8.86 (d, 1H, J=2 Hz), 9.10 (dd, 1H, J=2, 5 Hz), 9.59 (s, 1H); 31P (121.4 MHz, CD3OD) δ 20.0; MS (m/z) 660 [M+H]+.

Workup

  1. custompurified by RP HPLC
  2. customover 20 minutes

Sources & evidence

ORD record
ord-f262209b41d74b38a6197cc24fb9bd64
Source dataset
uspto-grants-2008_08
Patent number
US07417055B2

Reaction notes

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