Water → Tert-butyl 4-[(3-carbamoyl-8-iodo-4,5-dihydro-1H-pyrazolo[4,3-h]quinazolin-1-yl)methyl]piperidine-1-carboxylate

HRID 45796Notes

Reaction equation

HRID 45796 reaction equation
[I:1][C:2]1[N:11]=[CH:10][C:9]2[CH2:8][CH2:7][C:6]3[C:12]([C:15]([NH2:17])=[O:16])=[N:13][NH:14][C:5]=3[C:4]=2[N:3]=1.Br[CH2:19][CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[C:15]([C:12]1[C:6]2[CH2:7][CH2:8][C:9]3[CH:10]=[N:11][C:2]([I:1])=[N:3][C:4]=3[C:5]=2[N:14]([CH2:19][CH:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:27])[CH2:22][CH2:21]2)[N:13]=1)(=[O:16])[NH2:17]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 178513840HCID 178513840, compound

Product 1

HCID 86668391Tert-butyl 4-[(3-carbamoyl-8-iodo-4,5-dihydro-1H-pyrazolo[4,3-h]quinazolin-1-yl)methyl]piperidine-1-carboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 8-iodo-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (prepared following the method reported in WO2008074788A1) 50 mg, (0.146 mmol) in DMF (3 ml), tert-butyl 4-(bromomethyl)piperidine-1-carboxylate 61 mg, (0.219 mmol) and Cs2CO3 95 mg, (0.293 mmol), were added. The mixture was heated at 70° C. and stirred for 4 hours. The cooled mixture was treated with water (10 ml) and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over Na2SO4, and concentrated. The crude material was purified by flash chromatography eluting with DCM/EtOH 9/1 to afford the desired title product 63 mg (80%) as a white solid. LC/MS (254 nm) HPLC method 2 Rt 6.51 min. 1H NMR (401 MHz, DMSO-d6) δ 8.46 (s, 1H), 7.47 (s, 1H), 7.32 (s, 1H), 4.50-4.55 (m, 2H), 3.84-3.96 (m, 2H), 2.99-3.07 (m, 2H), 2.84-2.95 (m, 2H), 2.59-2.75 (m, 2H), 2.07 (s, 1H), 1.56 (br. s., 2H), 1.39 (s, 9H), 1.08-1.22 (m, 2H). HRMS (ESI) calcd for C21H27IN6O3 [M+H]+ 539.1262 found 539.1274.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase was washed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude material was purified by flash chromatography
  6. washeluting with DCM/EtOH 9/1

Sources & evidence

ORD record
ord-7fb34f1bed5647cd866beb3a9f1916cb
Source dataset
uspto-grants-2013_09
Patent number
US08541576B2

Reaction notes

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