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

HRID 451626Notes

Reaction equation

HRID 451626 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), 7.39 (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-cda1dd04e75145faba3cbfe30d32dd9d
Source dataset
uspto-grants-2013_07
Patent number
US08487116B2

Reaction notes

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