N-(tert-butoxycarbonyl)glycine → tert-butyl[2-({4-[3-carbamoyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazolin-1-yl]cyclohexyl}amino)-2-oxoethyl]carbamate

HRID 45803Notes

Reaction equation

HRID 45803 reaction equation
Cl.[NH2:2][CH:3]1[CH2:8][CH2:7][CH:6]([N:9]2[C:21]3[C:20]4[N:19]=[C:18]([S:22][CH3:23])[N:17]=[CH:16][C:15]=4[CH:14]=[CH:13][C:12]=3[C:11]([C:24]([NH2:26])=[O:25])=[N:10]2)[CH2:5][CH2:4]1.[C:27]([O:31][C:32]([NH:34][CH2:35][C:36](O)=[O:37])=[O:33])([CH3:30])([CH3:29])[CH3:28].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C([O-])(O)=O.[Na+]>CC(N(C)C)=O.C(OCC)(=O)C>[C:27]([O:31][C:32](=[O:33])[NH:34][CH2:35][C:36]([NH:2][CH:3]1[CH2:8][CH2:7][CH:6]([N:9]2[C:21]3[C:20]4[N:19]=[C:18]([S:22][CH3:23])[N:17]=[CH:16][C:15]=4[CH:14]=[CH:13][C:12]=3[C:11]([C:24](=[O:25])[NH2:26])=[N:10]2)[CH2:5][CH2:4]1)=[O:37])([CH3:30])([CH3:28])[CH3:29]

Participants

8

Reactant 5

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67975581HCID 67975581, compound

Product 1

HCID 68068853tert-butyl[2-({4-[3-carbamoyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazolin-1-yl]cyclohexyl}amino)-2-oxoethyl]carbamateYield 81.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

30 mg (0.084 mmol) of 1-(4-aminocyclohexyl)-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide hydrochloride were dissolved in 2 ml of dimethyl acetamide. To the obtained solution 21 mg (0.126 mmol) of N-(tert-butoxycarbonyl)glycine, 60 μl (0.336 mmol) of DIPEA, 40 mg (0.126 mmol) of TBTU were added. The mixture was stirred at room temperature for 18 hours, the solution was portioned between ethyl acetate and saturated aqueous solution of NaHCO3, the organic layer was washed with brine, dried over Na2SO4 and evaporated under vacuum. The crude was purified by silica gel chromatography (DCM/MeOH/NH4OH 95/5/0.1) to provide tert-butyl[2-({4-[3-carbamoyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazolin-1-yl]cyclohexyl}amino)-2-oxoethyl]carbamate 35 mg (81%) as a white solid. 1H NMR (401 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.27 (d, J=8.67 Hz, 1H), 7.78 (d, J=6.35 Hz, 1H), 7.74 (d, J=8.67 Hz, 1H), 7.64 (br. s., 1H), 7.55 (br. s., 1H), 6.86 (t, J=5.86 Hz, 1H), 6.00 (br. s., 1H), 3.96 (d, J=2.56 Hz, 1H), 3.62 (d, J=5.61 Hz, 2H), 2.72 (s, 3H), 2.23-2.36 (m, 2H), 1.91-2.11 (m, 4H), 1.68-1.82 (m, 2H), 1.38 (s, 9H).

Workup

  1. washthe organic layer was washed with brine
  2. dry with materialdried over Na2SO4
  3. customevaporated under vacuum
  4. customThe crude was purified by silica gel chromatography (DCM/MeOH/NH4OH 95/5/0.1)

Sources & evidence

ORD record
ord-fe3680931c7146ddb0ae7c2a171512a9
Source dataset
uspto-grants-2013_09
Patent number
US08541576B2

Reaction notes

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