Sodium Hydroxide → HCID 68313427, compound

HRID 2404382Notes

Reaction equation

HRID 2404382 reaction equation
[F:1][C:2]1([F:15])[C@@H:7]2[C@H:3]1[C@@H:4]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:5][C@H:6]2[NH2:8].CCN(C(C)C)C(C)C.O=C1CCC(=O)N1[O:32][C:33]([NH:35][C:36]1[CH:44]=[CH:43][CH:42]=[C:41]2[C:37]=1[CH:38]=[N:39][N:40]2C(OC)=O)=O.[OH-].[Na+]>CCOC(C)=O.CO.CN(C=O)C>[F:1][C:2]1([F:15])[C@@H:7]2[C@H:3]1[C@@H:4]([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[CH2:5][C@H:6]2[NH:8][C:33]([NH:35][C:36]1[CH:44]=[CH:43][CH:42]=[C:41]2[C:37]=1[CH:38]=[N:39][NH:40]2)=[O:32]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 11313556methyl 4-({[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}amino)-1H-indazole-1-carboxylateHCID 68313495HCID 68313495, compound

Product 1

HCID 68313427HCID 68313427, compoundYield 86.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

An orange solution of Example 54C (77 mg, 0.368 mmol), DMF (0.8 mL), i-Pr2NEt (0.135 mL, 0.773 mmol), and methyl 4-((2,5-dioxopyrrolidin-1-yloxy)carbonylamino)-1H-indazole-1-carboxylate (128 mg, 0.386 mmol) was stirred at ambient temperature. After 15 minutes, MeOH (1.60 mL) and sodium hydroxide (50 wt % in water, 0.058 mL, 1.1 mmol) were added. After 20 minutes of stirring, the mixture was diluted with EtOAc (30 mL) and washed with water (10 mL) and brine (10 mL), dried (Na2SO4), and concentrated. The residue was purified by flash column chromatography (75-100% EtOAc/hexanes, gradient elution) to provide the title compound (117 mg, 0.318 mmol, 86% yield). 1H NMR (400 MHz, DMSO-d6) δ 13.01 (s, 1H), 8.72 (s, 1H), 8.03 (s, 1H), 7.58 (d, J=7.3 Hz, 1H), 7.47-7.30 (m, 4H), 7.30-7.14 (m, 2H), 7.07 (d, J=8.3 Hz, 1H), 6.48 (d, J=6.1 Hz, 1H), 4.30 (s, 1H), 3.54 (d, J=6.6 Hz, 1H), 2.64-2.50 (m, 3H), 1.81 (d, J=13.8 Hz, 1H). MS (DCI) M/Z 369 [M+H]+.

Workup

  1. washwashed with water (10 mL) and brine (10 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography (75-100% EtOAc/hexanes, gradient elution)

Sources & evidence

ORD record
ord-5565bf7f9a0a4712be0ec4fa6d37c2b1
Source dataset
uspto-grants-2014_08
Patent number
US08802711B2

Reaction notes

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