Sodium Hydroxide → HCID 68313584, compound

HRID 2404384Notes

Reaction equation

HRID 2404384 reaction equation
[C:1]1([C@@H:7]2[C@H:12]3[C@H:10]([CH2:11]3)[C@H:9]([NH2:13])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(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+]>CCOC(C)=O.CO.CN(C=O)C>[NH:38]1[C:39]2[C:35](=[C:34]([NH:33][C:31]([NH:13][C@@H:9]3[CH2:8][C@H:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[C@H:12]4[C@@H:10]3[CH2:11]4)=[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 68313623HCID 68313623, compound

Product 1

HCID 68313584HCID 68313584, compoundYield 72.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

An orange solution of Example 55C (20 mg, 0.115 mmol), DMF (1 mL), DIPEA (0.042 mL, 0.242 mmol), and methyl 4-((2,5-dioxopyrrolidin-1-yloxy)carbonylamino)-1H-indazole-1-carboxylate (40.3 mg, 0.121 mmol) was stirred at ambient temperature. After 15 minutes, MeOH (2.00 mL) and sodium hydroxide (50 wt % in water, 0.018 mL, 0.346 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 (27.5 mg, 0.083 mmol, 71.7% yield). 1H NMR (400 MHz, DMSO-d6) δ 13.0 (brs, 1H), 8.63 (s, 1H), 8.09 (d, J=1.0 Hz, 1H), 7.65 (d, J=7.6 Hz, 1H), 7.39-7.33 (m, 2H), 7.30 (t, J=7.5 Hz, 2H), 7.24-7.16 (m, 2H), 7.05 (d, J=8.2 Hz, 1H), 6.52 (d, J=7.6 Hz, 1H), 4.49-4.38 (m, 1H), 3.50-3.41 (m, 1H), 2.24 (dt, J=12.7, 7.6 Hz, 1H), 1.66-1.58 (m, 2H), 1.29-0.90 (m, 1H), 0.69 (q, J=4.2 Hz, 1H), 0.48 (td, J=7.7, 5.2 Hz, 1H). MS (DCI) M/Z 350 [M+NH4]+.

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-6fc914560c2745bd80ae5bd7d62f76b8
Source dataset
uspto-grants-2014_08
Patent number
US08802711B2

Reaction notes

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