Lithium Hydroxide → 2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(phosphonomethyl)phenylsulfonamido)acetic acid

HRID 1470088Notes

Reaction equation

HRID 1470088 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:15]=[C:16]([S:20]([N:23]([CH2:30][P:31](=[O:34])([OH:33])[OH:32])[CH2:24][C:25]([O:27]CC)=[O:26])(=[O:22])=[O:21])[CH:17]=[CH:18][CH:19]=1.[OH-].[Li+]>O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:15]=[C:16]([S:20]([N:23]([CH2:24][C:25]([OH:27])=[O:26])[CH2:30][P:31]([OH:34])([OH:33])=[O:32])(=[O:22])=[O:21])[CH:17]=[CH:18][CH:19]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67461069(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(2-ethoxy-2-oxoethyl)phenylsulfonamido)methylphosphonic acid2×

Product 1

HCID 674592992-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(phosphonomethyl)phenylsulfonamido)acetic acidYield 35%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

Into a 50-mL round-bottom flask, was placed a solution of (3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(2-ethoxy-2-oxoethyl)phenylsulfonamido)methylphosphonic acid (Intermediate 8.4) (180 mg, 0.33 mmol, 1.00 equiv) in tetrahydrofuran/water (5/5 mL). This was followed by the addition of lithium hydroxide (39 mg, 1.62 mmol, 4.97 equiv) in several batches at room temperature. The resulting solution was stirred for 4 h at room temperature. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The pH value of the solution was adjusted to 6 with 1M hydrogen chloride. The resulting mixture was concentrated under vacuum. The crude product (150 mg) was purified by preparative HPLC giving 59.2 mg (35%) of the title compound as a TFA salt. 1H-NMR (300 MHz, DMSO+D2O, ppm): 7.73˜7.74 (m, 1H), 7.67˜7.68 (m, 1H), 7.58˜7.62 (m, 2H), 7.49 (s, 1H), 7.00 (s, 1H), 4.71˜4.75 (m, 1H), 4.49 (d, J=16.2 Hz, 1H), 4.33 (d, J=15.9 Hz, 1H), 4.07 (s, 2H), 3.62˜3.64 (m, 1H), 3.45˜3.54 (m, 2H), 3.31˜3.40 (m, 1H), 2.88 (s, 3H). MS (ES, m/z): 523 [M+H]+.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. customThe crude product (150 mg) was purified by preparative HPLC

Sources & evidence

ORD record
ord-739824c4fb164b1ba9a4e09bc37e7777
Source dataset
uspto-grants-2015_04
Patent number
US09006281B2

Reaction notes

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