Sodium Hydroxide → N-(5-{4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenylsulfamoyl}-4-methyl-thiazol-2-yl)-acetamide

HRID 858055Notes

Reaction equation

HRID 858055 reaction equation
[C:1]([NH:4][C:5]1[S:6][C:7]([S:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C:22]([NH:24][C:25]3[C:26](=[O:45])[N:27]([CH2:37][C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=4[F:44])[C:28](=[O:36])[N:29]([CH2:32][CH:33]4[CH2:35][CH2:34]4)[C:30]=3[NH2:31])=O)=[CH:17][CH:16]=2)(=[O:13])=[O:12])=[C:8]([CH3:10])[N:9]=1)(=[O:3])[CH3:2].[OH-].[Na+]>CO>[CH:33]1([CH2:32][N:29]2[C:30]3[N:31]=[C:22]([CH2:21][C:18]4[CH:19]=[CH:20][C:15]([NH:14][S:11]([C:7]5[S:6][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[N:9][C:8]=5[CH3:10])(=[O:12])=[O:13])=[CH:16][CH:17]=4)[NH:24][C:25]=3[C:26](=[O:45])[N:27]([CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[F:44])[C:28]2=[O:36])[CH2:34][CH2:35]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 587628482-[4-(2-acetylamino-4-methyl-thiazole-5-sulfonylamino)-phenyl]-N-[6-amino-1-cyclopropylmethyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetamide

Product 1

HCID 10258558N-(5-{4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenylsulfamoyl}-4-methyl-thiazol-2-yl)-acetamideYield 29.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 2-[4-(2-acetylamino-4-methyl-thiazole-5-sulfonylamino)-phenyl]-N-[6-amino-1-cyclopropylmethyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetamide (56 mg, 0.085 mmol) in methanol warmed to 50° C. was treated with a 10% aqueous sodium hydroxide solution (0.34 mL, 0.085 mmol). The reaction was stirred at 50° C. for 6 h. At this time, the reaction was concentrated in vacuo, diluted with water, and acidified to pH=2 with a 1.0N aqueous hydrochloric acid solution (0.9 mL). This mixture was cooled in an ice-bath. The resulting solids were collected by filtration, washed with water, and dried in vacuo. HPLC (20–80% acetonitrile/water) afforded N-(5-{4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenylsulfamoyl}-4-methyl-thiazol-2-yl)-acetamide (16.1 mg, 29.7%) as a white solid; FAB-HRMS m/e calculated for C29H28FN7O5S2 (M+H)+ 638.1656, found 638.1641; and 2-amino-4-methyl-thiazole-5-sulfonic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-amide trifluoro-acetic acid salt (5.4 mg, 10%) as a white solid; FAB-HRMS m/e calculated for C27H26FN7O4S2 (M+H)+ 596.1550, found 596.1547.

Workup

  1. concentrationAt this time, the reaction was concentrated in vacuo
  2. additiondiluted with water
  3. temperatureThis mixture was cooled in an ice-bath
  4. filtrationThe resulting solids were collected by filtration
  5. washwashed with water
  6. customdried in vacuo

Sources & evidence

ORD record
ord-3737728ff1b242ff88224a40b4d549e2
Source dataset
uspto-grants-2006_12
Patent number
US07148229B2

Reaction notes

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