Azetidine → HCID 70496750, compound

HRID 1466605Notes

Reaction equation

HRID 1466605 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C:8]2[NH:12][N:11]=[CH:10][C:9]=2[NH:13][C:14]([C:16]2C=NN3C=C[CH:22]=[N:21][C:20]=23)=[O:15])[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:34][C@@H:35]1[CH2:37][O:36]1.[NH:38]1[CH2:41][CH2:40][CH2:39]1>CN(C)C=O>[N:38]1([CH2:34][C@H:35]([OH:36])[CH2:37][N:11]2[CH:10]=[C:9]([NH:13][C:14]([C:16]3[C:20]4[N:21]=[CH:22][N:13]=[CH:9][C:10]=4[NH:11][N:12]=3)=[O:15])[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[O:25][CH3:26])=[N:12]2)[CH2:41][CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 10422AzetidineHCID 10796Cesium carbonateHCID 149428(+)-EpichlorohydrinHCID 66850618HCID 66850618, compound

Product 1

HCID 70496750HCID 70496750, compoundYield 20.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of N-(5-(5-chloro-2-methoxyphenyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (60 mg, 0.16 mmol) and cesium carbonate (212 mg, 0.65 mmol) in N,N-Dimethylformamide (1 mL) was added (S)-2-(chloromethyl)oxirane (26.3 mg, 0.28 mmol). The reaction mixture was stirred for 8 hours at room temperature, at which time LCMS analysis showed complete consumption of starting material. Azetidine (44 uL, 0.65 mmol) was added and the reaction mixture was stirred for an additional 16 hours at room temperature. The reaction mixture was filtered and purified by reverse phase HPLC to afford the title compound as a white solid (7.8 mg). LCMS (ESI) m+H=482.2; 1H NMR (400 MHz, DMSO) δ 9.69 (s, 1H), 9.34 (dd, J=7.0, 1.6, 1H), 8.78 (dd, J=4.2, 1.6, 1H), 8.66 (s, 1H), 8.27 (s, 1H), 7.50 (dd, J=8.9, 2.7, 1H), 7.40 (d, J=2.7, 1H), 7.33-7.26 (m, 2H), 4.94 (d, J=5.4, 1H), 4.21 (dd, J=13.7, 3.8, 1H), 3.99 (dd, J=13.8, 7.8, 1H), 3.84 (s, 3H), 3.77 (s, 1H), 3.17 (t, J=6.9, 4H), 2.39 (qd, J=12.0, 5.9, 2H), 2.02-1.93 (m, 2H).

Workup

  1. customconsumption of starting material
  2. stirringthe reaction mixture was stirred for an additional 16 hours at room temperature
  3. filtrationThe reaction mixture was filtered
  4. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-ef38d8bbccde4e5fbe61c215853d65c2
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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