Diisopropylethylamine → (S)-4-(5-chloro-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3-methylmorpholine

HRID 72181

Reaction equation

HRID 72181 reaction equation
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[N:10]([CH3:11])[N:9]=[CH:8][C:6]=2[N:7]=1.C(N(CC)C(C)C)(C)C.[CH3:22][C@H:23]1[CH2:28][O:27][CH2:26][CH2:25][NH:24]1>CN(C=O)C.CCOCC>[Cl:1][C:2]1[N:3]=[C:4]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][C@@H:23]2[CH3:22])[C:5]2[N:10]([CH3:11])[N:9]=[CH:8][C:6]=2[N:7]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 12012220(3S)-3-methylmorpholineHCID 574158625,7-dichloro-1-methyl-1H-pyrazolo[4,3-d]pyrimidine

Product 1

HCID 58222518(S)-4-(5-chloro-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3-methylmorpholineYield 93.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5,7-dichloro-1-methyl-1H-pyrazolo[4,3-d]pyrimidine (200.0 mg, 0.98 mmol) in anhydrous DMF (2 mL) was added N,N-diisopropylethylamine (0.21 mL, 1.18 mmol, 1.2 eq.) followed by (S)-3-methylmorpholine (199.3 mg, 1.9 mmol, 2.0 eq.). The reaction mixture was stirred at RT under N2 for 4 h and diluted with ether (50 mL). The organic layer was washed with saturated aqueous solution of sodium bicarbonate, water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in heptane) to afford the desired product (k-1) as a foam (245.4 mg, 93.0%). 1H NMR (CDCl3, 500 MHz) δ ppm 8.03 (s, 1H), 4.21 (broad d, J=6.2 Hz, 1H), 4.15 (s, 3H), 3.97 (d, J=10.7 Hz, 1H), 3.90 (d, J=9.8 Hz, 1H), 3.81 to 3.65 (m, 3H), 3.56 (d, J=12.4 Hz, 1H), 1.38 (d, J=6.6 Hz, 3H); LC-MS m/z (method A)=268 [M+H]+, RT=1.71 min.

Workup

  1. washThe organic layer was washed with saturated aqueous solution of sodium bicarbonate, water and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-6509c6b03059425bb28feba1c042a567
Source dataset
uspto-grants-2014_09
Patent number
US08828990B2

Linked notes

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