Methanol → 1-(1H-Indazol-4-yl)-3-(4-piperidin-1-yl-indan-1-yl)-urea

HRID 451622Notes

Reaction equation

HRID 451622 reaction equation
COC([N:5]1[C:13]2[C:8](=[C:9]([NH:14][C:15]([O:17]N3C(=O)CCC3=O)=O)[CH:10]=[CH:11][CH:12]=2)[CH:7]=[N:6]1)=O.[N:25]1([C:31]2[CH:39]=[CH:38][CH:37]=[C:36]3[C:32]=2[CH2:33][CH2:34][CH:35]3[NH2:40])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.CCN(C(C)C)C(C)C.CO>CN(C=O)C.O>[NH:5]1[C:13]2[C:8](=[C:9]([NH:14][C:15]([NH:40][CH:35]3[C:36]4[C:32](=[C:31]([N:25]5[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]5)[CH:39]=[CH:38][CH:37]=4)[CH2:33][CH2:34]3)=[O:17])[CH:10]=[CH:11][CH:12]=2)[CH:7]=[N:6]1

Participants

7

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 11313556methyl 4-({[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}amino)-1H-indazole-1-carboxylateHCID 671879554-Piperidin-1-ylindan-1-ylamine

Product 1

HCID 112342231-(1H-Indazol-4-yl)-3-(4-piperidin-1-yl-indan-1-yl)-ureaYield 93.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 6228DimethylformamideSolvent

Procedure

4-(2,5-Dioxopyrrolidin-1-yl-oxycarbonylamino)-indazole-1-carboxylic acid methyl ester (5.57 g, 16.8 mmol) was added to a solution of 4-piperidin-1-ylindan-1-ylamine (3.81 g, 17.6 mmol) and DIPEA (3.0 mL, 17.2 mmol) in DMF (80 mL) under nitrogen atmosphere at ambient temperature. After 30 minutes the reaction solution was diluted with water (350 mL), the resulting beige precipitate was filtered off, washed with water and air-dried. The wet cake was added to a solution of methanol (200 mL), water (3 mL) and TEA (7.0 mL, 50.2 mmol). The mixture was refluxed for 90 minutes, cooled to room temperature, diluted with water (200 mL), collected the beige precipitate by filtration, rinsed with water and air-dried. The wet cake was vacuum dried to constant weight, yielding 1-(1H-indazol-4-yl)-3-(4-piperidin-1-ylindan-1-yl)-urea (5.89 g, 93%) as a beige solid. MS (ESI) m/z: 376.00 [M+H]+. 1H NMR (DMSO-d6) δ: 1.56 (m, 2H), 1.65 (m, 4H), 1.78 (m, 1H), 2.44 (m, 1H), 2.77 (m, 1H), 2.85 (m, 3H), 2.95 (m, 2H), 5.16 (q, 1H), 6.66 (d, 1H), 6.81 (d, 1H), 6.95 (d, 1H), 7.07 (d, 1H), 7.22 (m, 2H), 7.68 (d, 1H), 8.05 (s, 1H), 8.62 (s, 1H), 13.00 (s, 1H). Anal Calcd for C22H25N5O: C, 70.38; H, 6.71; N, 18.65. Found: C, 70.24; H, 6.72; N, 18.47.

Workup

  1. filtrationthe resulting beige precipitate was filtered off
  2. washwashed with water
  3. customair-dried
  4. temperatureThe mixture was refluxed for 90 minutes
  5. customcollected the beige precipitate
  6. filtrationby filtration
  7. washrinsed with water
  8. customair-dried
  9. customdried to constant weight

Sources & evidence

ORD record
ord-b7841f0b55964213983a458122162385
Source dataset
uspto-grants-2013_07
Patent number
US08487116B2

Reaction notes

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