Thionyl Chloride → (6aR,9aS)-5,6a,7,8,9,9a-hexahydro-5-methyl-3-(phenylamino)-cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(2H)-one

HRID 72693Notes

Reaction equation

HRID 72693 reaction equation
S(Cl)(Cl)=O.O[C@@H:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[NH:11][C:12]1[N:13]([CH3:29])[C:14](=[O:28])[C:15]2[C:16](=[N:18][NH:19][C:20]=2[NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:17]=1>C(Cl)Cl>[CH3:29][N:13]1[C:14](=[O:28])[C:15]2=[C:20]([NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[NH:19][N:18]=[C:16]2[N:17]2[C@H:6]3[CH2:10][CH2:9][CH2:8][C@H:7]3[N:11]=[C:12]12

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 684983116-((1R,2R)-2-hydroxycyclopentylamino)-5-methyl-3-(phenylamino)-2H-pyrazolo[3,4-d]pyrimidin-4(5H)-one

Product 1

HCID 59548046(6aR,9aS)-5,6a,7,8,9,9a-hexahydro-5-methyl-3-(phenylamino)-cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(2H)-oneYield 87.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2.0 M solution of thionyl chloride in CH2Cl2 (7.5 mL, 15.4 mmol) is added dropwise to a solution of 6-((1R,2R)-2-hydroxycyclopentylamino)-5-methyl-3-(phenylamino)-2H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (3.5 g, 10.3 mmol) in CH2Cl2 (30 mL) at room temperature. After the completion of the addition, the reaction mixture is stirred at r.t. for 2 h. Solvent and excess SOCl2 are removed under reduced pressure. The residue is suspended in water (100 mL), and then carefully neutralized with 7% ammonium hydroxide (5 mL) to pH=6.5˜7. The mixture is extracted with CH2Cl2 and MeOH (10:1, v/v) five times. The combined organic phase is washed with water, dried over Na2SO4, and then evaporated under reduced vacuum to give 2.9 g of crude product. MS (ESI) m/z 323.2 [M+H]+.

Workup

  1. additionAfter the completion of the addition
  2. customSolvent and excess SOCl2 are removed under reduced pressure
  3. extractionThe mixture is extracted with CH2Cl2 and MeOH (10:1
  4. washThe combined organic phase is washed with water
  5. dry with materialdried over Na2SO4
  6. customevaporated under reduced vacuum

Sources & evidence

ORD record
ord-0674ab7c1d75487aa0d02fabc83fc01e
Source dataset
uspto-grants-2014_09
Patent number
US08829008B2

Reaction notes

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