Methyl Carbamate → HCID 66549081, compound

HRID 2404391Notes

Reaction equation

HRID 2404391 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]1[CH2:12][CH2:11][CH:10]([NH2:13])[CH2:9]1.C(N(CC)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:32].C(=O)(OC)N.[OH-].[Na+]>O.CO.CN(C=O)C>[C:31](=[O:32])=[O:30].[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]1[CH2:12][CH2:11][C@@H:10]([NH:13][C:31]([NH:33][C:34]2[CH:42]=[CH:41][CH:40]=[C:39]3[C:35]=2[CH:36]=[N:37][NH:38]3)=[O:30])[CH2:9]1

Participants

10

Reactant 5

HCID 11722Methyl CarbamateHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 11313556methyl 4-({[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}amino)-1H-indazole-1-carboxylateHCID 68313587HCID 68313587, compound

Product 2

HCID 280Carbon DioxideHCID 66549081HCID 66549081, compoundYield 91.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of Example 61B (0.35 g, 1.95 mmol), DMF (10 mL), N,N-diisopropyl ethylamine (0.72 mL, 4.1 mmol) and methyl 4-((2,5-dioxopyrrolidin-1-yloxy)carbonylamino)-1H-indazole-1-carboxylate (prepared as in Org. Proc. Res. Dev., 2007, 11, 578; 0.65 g, 1.95 mmol) was stirred at ambient temperature. After 5 minutes, LCMS showed complete conversion to the methyl carbamate intermediate. Methanol (20 mL) and 2N sodium hydroxide (5.86 mmol) were added resulting in a white slurry. The mixture was diluted with water and extracted with ethyl acetate (100 mL). The organic extract was washed with brine (50 mL), dried (Na2SO4), filtered and concentrated. The mixture was separated using a Chiralpak AD-H column and eluting with 5-50% MeOH:CO2 10 min at 3 mL/min to provide the title compound (303 mg, 31%) and Example 62 (181 mg, 27%). Data for Example 61C: 1H NMR (300 MHz, DMSO-d6) δ 12.98 (bs, 1H), 8.56 (s, 1H), 8.07 (d, J=1.0 Hz, 1H), 7.62 (d, J=7.9 Hz, 1H), 7.46-7.36 (m, 1H), 7.32-7.01 (m, 5H), 6.55 (d, J=7.2 Hz, 1H), 4.23-3.99 (m, 3H), 2.16-1.97 (m, 2H), 1.82-1.46 (m, 3H). MS (ESI+) M/Z 339 (M+H)+.

Workup

  1. customresulting in a white slurry
  2. extractionextracted with ethyl acetate (100 mL)
  3. extractionThe organic extract
  4. washwas washed with brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe mixture was separated
  9. washeluting with 5-50% MeOH

Sources & evidence

ORD record
ord-ada8c79a21ae455c82154d7d1e22294d
Source dataset
uspto-grants-2014_08
Patent number
US08802711B2

Reaction notes

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