Methanol → 1-[5-(2-cyanopropan-2-yl)-2,3-dihydro-1H-inden-1-yl]-3-(1H-indazol-4-yl)urea

HRID 2223418Notes

Reaction equation

HRID 2223418 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.[NH2:25][CH:26]1[C:34]2[C:29](=[CH:30][C:31]([C:35]([CH3:39])([CH3:38])[C:36]#[N:37])=[CH:32][CH:33]=2)[CH2:28][CH2:27]1.CCN(C(C)C)C(C)C.CO>CN(C=O)C.O>[C:36]([C:35]([C:31]1[CH:30]=[C:29]2[C:34](=[CH:33][CH:32]=1)[CH:26]([NH:25][C:15]([NH:14][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]3[C:8]=1[CH:7]=[N:6][NH:5]3)=[O:17])[CH2:27][CH2:28]2)([CH3:39])[CH3:38])#[N:37]

Participants

7

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 11313556methyl 4-({[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}amino)-1H-indazole-1-carboxylateHCID 671892902-(1-Aminoindan-5-yl)-2-methylpropionitrile

Product 1

HCID 671873051-[5-(2-cyanopropan-2-yl)-2,3-dihydro-1H-inden-1-yl]-3-(1H-indazol-4-yl)ureaYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 6228DimethylformamideSolvent

Procedure

4-(2,5-Dioxopyrrolidin-1-yl-oxycarbonylamino)-indazole-1-carboxylic acid methyl ester (3.31 g, 9.96 mmol) was added to a solution of 2-(1-aminoindan-5-yl)-2-methylpropionitrile (2.09 g, 10.5 mmol) and DIPEA (1.8 mL, 10.3 mmol) in DMF (40 mL) under nitrogen atmosphere at ambient temperature. After 1 hour the reaction solution was diluted with water (200 mL), the resulting white precipitate was filtered off, washed with water and air-dried. The wet cake was added to a solution of methanol (100 mL), water (3 mL) and TEA (2.8 mL, 20.1 mmol). The mixture was refluxed for 30 minutes, cooled the solution to room temperature, diluted with water (500 mL), collected the white precipitate by filtration, rinsed with water and air-dried. The wet cake was vacuum dried to constant weight, yielding 1-[5-(cyano-isopropyl)-indan-1-yl]-3-(1H-indazol-4-yl)-urea (3.32 g, 93%) as a white solid. MS (ESI) m/z: 360.07 [M+H]+. 1H NMR (DMSO-d6) δ: 1.69 (s, 6H), 1.87 (m, 1H), 2.47 (m, 1H), 2.89 (m, 1H), 2.98 (m, 1H), 5.19 (q, 1H), 6.73 (d, 1H), 7.08 (d, 1H), 7.22 (t, 1H). Anal (s, 2H), 7.44 (s, 1H), 7.66 (d, 1H), 8.04 (s, 1H), 8.59 (s, 1H), 13.00 (s, 1H). Anal Calcd for C21H21N5O.0.4H2O: C, 68.80; H, 5.99; N, 19.10. Found: C, 68.94; H, 5.72; N, 18.95.

Workup

  1. filtrationthe resulting white precipitate was filtered off
  2. washwashed with water
  3. customair-dried
  4. temperatureThe mixture was refluxed for 30 minutes
  5. customcollected the white precipitate
  6. filtrationby filtration
  7. washrinsed with water
  8. customair-dried
  9. customdried to constant weight

Sources & evidence

ORD record
ord-895d4eda7b114d31a9f6aa7b5e1fac6a
Source dataset
uspto-grants-2008_05
Patent number
US07375126B2

Reaction notes

Loading…