Dimethylformamide → HCID 71715942, compound

HRID 928253Notes

Reaction equation

HRID 928253 reaction equation
[OH:1][C@@H:2]1[C@H:6]([OH:7])[C@@H:5]([CH2:8][O:9][S:10](=[O:13])(=[O:12])[NH2:11])[CH2:4][C@H:3]1[NH:14][C:15]1[N:20]2[N:21]=[C:22]([C:24]3[CH:33]=[CH:32][CH:31]=[C:30]4[C:25]=3[CH:26]=[CH:27][C:28]([C:34]([O:36]C)=[O:35])=[CH:29]4)[CH:23]=[C:19]2[N:18]=[CH:17][CH:16]=1.CN(C=O)C.[OH-].[Na+]>>[OH:1][C@@H:2]1[C@H:6]([OH:7])[C@@H:5]([CH2:8][O:9][S:10](=[O:13])(=[O:12])[NH2:11])[CH2:4][C@H:3]1[NH:14][C:15]1[N:20]2[N:21]=[C:22]([C:24]3[CH:33]=[CH:32][CH:31]=[C:30]4[C:25]=3[CH:26]=[CH:27][C:28]([C:34]([OH:36])=[O:35])=[CH:29]4)[CH:23]=[C:19]2[N:18]=[CH:17][CH:16]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 71715712HCID 71715712, compound

Product 1

HCID 71715942HCID 71715942, compoundYield 8.6%

Procedure

To a solution of (rac)-methyl rel-5-[7-({(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoyloxy)methyl]cyclopentyl}amino)pyrazolo[1,5-a]pyrimidin-2-yl]-2-naphthoate (0.048 g, 0.091 mmol) in DMF (2.0 mL, 26 mmol) is added 1.0 M NaOH (1.0 mL, 1.0 mmol). The mixture is stirred at room temperature for 1.5 hr and then concentrated in vacuo as an azeotropic mixture with toluene. The crude material is purified by preparative HPLC to provide (rac)-rel-5-[7-({(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoyloxy)methyl]cyclopentyl}amino)pyrazolo[1,5-a]pyrimidin-2-yl]-2-naphthoic acid (4.0 mg, yield 8.5%). LCMS: (AA) M+1 514; 1H NMR (400 MHz, DMSO) δ 8.71-8.63 (m, 1H), 8.55 (d, J=8.9 Hz, 1H), 8.25-8.16 (m, 2H), 8.09-7.98 (m, 1H), 7.98-7.90 (m, 1H), 7.89-7.79 (m, 1H), 7.75-7.63 (m, 1H), 7.55-7.25 (m, 1H), 6.79 (s, 1H), 6.33 (d, J=5.4 Hz, 1H), 5.2-4.6 (m, 2H), 4.18-4.05 (m, 1H), 4.06-3.90 (m, 3H), 3.80-3.68 (m, 1H), 2.40-2.15 (m, 2H), 1.56-1.36 (m, 1H).

Workup

  1. concentrationconcentrated in vacuo as an azeotropic mixture with toluene
  2. customThe crude material is purified by preparative HPLC

Sources & evidence

ORD record
ord-eba7bfba2dc349ad817f8fd657c84322
Source dataset
uspto-grants-2016_03
Patent number
US09290500B2

Reaction notes

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