Sodium Hydroxide → 1-(1H-indazol-4-yl)-3-[(cis)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentyl]urea

HRID 2404395Notes

Reaction equation

HRID 2404395 reaction equation
Cl.[CH3:2][C:3]1[N:4]=[C:5]([C@@H:8]2[CH2:12][CH2:11][C@H:10]([NH2:13])[CH2:9]2)[S:6][CH:7]=1.C(N(C(C)C)CC)(C)C.O=C1CCC(=O)N1[O:30][C:31]([NH:33][C:34]1[CH:42]=[CH:41][CH:40]=[C:39]2[C:35]=1[CH:36]=[N:37][N:38]2C(OC)=O)=O.[OH-].[Na+]>O.CO.CN(C)C=O>[NH:38]1[C:39]2[C:35](=[C:34]([NH:33][C:31]([NH:13][C@H:10]3[CH2:11][CH2:12][C@@H:8]([C:5]4[S:6][CH:7]=[C:3]([CH3:2])[N:4]=4)[CH2:9]3)=[O:30])[CH:42]=[CH:41][CH:40]=2)[CH:36]=[N:37]1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 11313556methyl 4-({[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}amino)-1H-indazole-1-carboxylateHCID 68313423(cis)-3-(4-Methylthiazol-2-yl)cyclopentanamine hydrochloride

Product 1

HCID 683134971-(1H-indazol-4-yl)-3-[(cis)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentyl]ureaYield 43%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of Example 120C (89 mg, 0.41 mmol), N,N-dimethylformamide (3 mL), diisopropylethylamine (0.15 mL, 0.85 mmol) and methyl 4-((2,5-dioxopyrrolidin-1-yloxy)carbonylamino)-1H-indazole-1-carboxylate (prepared as in Org. Proc. Res. Dev., 2007, 11, 578; 135 mg, 0.41 mmol) was stirred at room temperature for 10 minutes. Methanol (6 mL) and 5N aqueous NaOH (0.24 mL, 1.2 mmol) were added and stirring continued for 2 hours at room temperature. The reaction mixture was diluted with water (10 mL), concentrated to half the volume, and extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% of methanol/ethyl acetate (1:10) in hexanes) to obtain the title compound (60 mg, 43%) and Example 119 (28 mg, 20%). MS (ESI+) M/Z 342 [M+H]+.

Workup

  1. concentrationconcentrated to half the volume
  2. extractionextracted with ethyl acetate (2×20 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-6caad1df016e438192b853c824a83b80
Source dataset
uspto-grants-2014_08
Patent number
US08802711B2

Reaction notes

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