Hydrochloric Acid → 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

HRID 858054Notes

Reaction equation

HRID 858054 reaction equation
[NH2:1][C:2]1[N:7]([CH2:8][CH:9]2[CH2:11][CH2:10]2)[C:6](=[O:12])[N:5]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])[C:4](=[O:21])[C:3]=1[NH:22][C:23](=[O:32])[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([NH2:31])=[CH:27][CH:26]=1.[C:33]([NH:36][C:37]1[S:38][C:39]([S:43](Cl)(=[O:45])=[O:44])=[C:40]([CH3:42])[N:41]=1)(=[O:35])[CH3:34].C(Cl)Cl.Cl>N1C=CC=CC=1>[C:33]([NH:36][C:37]1[S:38][C:39]([S:43]([NH:31][C:28]2[CH:27]=[CH:26][C:25]([CH2:24][C:23]([NH:22][C:3]3[C:4](=[O:21])[N:5]([CH2:13][C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=4[F:20])[C:6](=[O:12])[N:7]([CH2:8][CH:9]4[CH2:11][CH2:10]4)[C:2]=3[NH2:1])=[O:32])=[CH:30][CH:29]=2)(=[O:44])=[O:45])=[C:40]([CH3:42])[N:41]=1)(=[O:35])[CH3:34]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 969512-Acetamido-4-methylthiazole-5-sulfonyl chlorideHCID 58762830N-[6-amino-1-cyclopropylmethyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-2-(4-amino-phenyl)-acetamide

Product 1

HCID 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]-acetamideYield 54%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

A solution of N-[6-amino-1-cyclopropylmethyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-2-(4-amino-phenyl)-acetamide (prepared as in Example 1, 75 mg, 0.16 mmol) in pyridine (1.6 mL) was stirred at 25° C. for 5 min. This solution was then treated with 2-acetylamino-4-methyl-thiazole-5-sulfonyl chloride (44 mg, 0.17 mmol). The reaction mixture was stirred at 25° C. for 24 h. The reaction mixture was then poured into a mixture of methylene chloride (50 mL) and a 1.0N aqueous hydrochloric acid solution (10 mL). This mixture was extracted with a 1/9 methanol/methylene chloride solution (1×50 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 7/93 methanol/methylene chloride) afforded 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 (56.4 mg, 54%) as an off-white solid; FAB-HRMS m/e calculated for C29H30FN7O6S2 (M+) 655.1683, found 655.1679

Workup

  1. extractionThis mixture was extracted with a 1/9 methanol/methylene chloride solution (1×50 mL)
  2. dry with materialThe organics were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-30cff64ee4b5482c9928435dfc38f9c5
Source dataset
uspto-grants-2006_12
Patent number
US07148229B2

Reaction notes

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