Methyl Carbamate → 1-(1H-indazol-4-yl)-3-[(1S,4R)-4-phenylcyclopent-2-en-1-yl]urea

HRID 2404378Notes

Reaction equation

HRID 2404378 reaction equation
[C:1]1([C@@H:7]2[CH2:11][C@H:10]([NH2:12])[CH:9]=[CH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)CC)(C)C.O=C1CCC(=O)N1[O:29][C:30]([NH:32][C:33]1[CH:41]=[CH:40][CH:39]=[C:38]2[C:34]=1[CH:35]=[N:36][N:37]2C(OC)=O)=O.C(=O)(OC)N.[OH-].[Na+]>O.CO.CN(C=O)C>[NH:37]1[C:38]2[C:34](=[C:33]([NH:32][C:30]([NH:12][C@H:10]3[CH2:11][C@@H:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH:8]=[CH:9]3)=[O:29])[CH:41]=[CH:40][CH:39]=2)[CH:35]=[N:36]1

Participants

9

Reactant 5

HCID 11722Methyl CarbamateHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 11313556methyl 4-({[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}amino)-1H-indazole-1-carboxylateHCID 68313332(1S,4R)-4-phenylcyclopent-2-enamine

Product 1

HCID 665512831-(1H-indazol-4-yl)-3-[(1S,4R)-4-phenylcyclopent-2-en-1-yl]ureaYield 71%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of Example 48C (455 mg, 2.86 mmol), DMF (8 mL), diisopropylethylamine (1.05 mL, 6.01 mmol), and methyl 4-((2,5-dioxopyrrolidin-1-yloxy)carbonylamino)-1H-indazole-1-carboxylate (prepared as in Org. Proc. Res. Dev., 2007, 950 mg, 2.86 mmol) was stirred at room temperature. After 15 minutes, LCMS showed complete conversion to methyl carbamate. Methanol (16 mL) and 50% aqueous sodium hydroxide (0.50 mL, 8.6 mmol) were added to the reaction mixture. After 10 minutes, LCMS showed complete conversion to product. Water (24 mL) was added dropwise, and the resulting white slurry was stirred at room temperature for 15 minutes. The slurry was filtered and washed with 1:1 MeOH/water (10 mL). The white solid was dried in a vacuum oven at 50° C. to provide the title compound (646 mg, 2.03 mmol, 71% over three steps). 1H NMR (300 MHz, DMSO-d6) δ 13.11-12.64 (m, 1H), 8.56 (s, 1H), 8.06 (d, J=0.9 Hz, 1H), 7.63 (d, J=7.4 Hz, 1H), 7.52-7.30 (m, 2H), 7.21 (m, 4H), 7.05 (d, J=8.3 Hz, 1H), 6.59 (d, J=8.1 Hz, 1H), 5.93 (s, 2H), 4.86 (q, J=7.8 Hz, 1H), 3.86 (t, J=7.3 Hz, 1H), 2.90 (dt, J=13.1, 8.2 Hz, 1H), 1.47-1.28 (m, 1H); MS (DCI) m/z 319 (M+H)+.

Workup

  1. waitAfter 10 minutes
  2. filtrationThe slurry was filtered
  3. washwashed with 1:1 MeOH/water (10 mL)
  4. customThe white solid was dried in a vacuum oven at 50° C.

Sources & evidence

ORD record
ord-5d58b49fa51f46f78dd7bd5d72788e5e
Source dataset
uspto-grants-2014_08
Patent number
US08802711B2

Reaction notes

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