Water → N-methyl-N-(pyrrolidin-3-ylmethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.5]octane-8-sulfonamide

HRID 589952Notes

Reaction equation

HRID 589952 reaction equation
C(OC([N:8]1[C:12]2[N:13]=[CH:14][N:15]=[C:16]([N:17]3[CH2:24][C:21]4([CH2:23][CH2:22]4)[N:20]([S:25](=[O:29])(=[O:28])[NH:26][CH3:27])[CH2:19][CH2:18]3)[C:11]=2[CH:10]=[CH:9]1)=O)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:37][CH:38]1[CH2:42][CH2:41][N:40](C(OC(C)(C)C)=O)[CH2:39]1.O>CN(C=O)C>[CH3:27][N:26]([CH2:37][CH:38]1[CH2:42][CH2:41][NH:40][CH2:39]1)[S:25]([N:20]1[C:21]2([CH2:23][CH2:22]2)[CH2:24][N:17]([C:16]2[C:11]3[CH:10]=[CH:9][NH:8][C:12]=3[N:13]=[CH:14][N:15]=2)[CH2:18][CH2:19]1)(=[O:28])=[O:29]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 24730280tert-Butyl 3-(bromomethyl)pyrrolidine-1-carboxylateHCID 682959194-(4-Methylsulfamoyl-4,7-diaza-spiro[2.5]oct-7-yl)-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid tert-butyl ester2×

Product 1

HCID 57410097N-methyl-N-(pyrrolidin-3-ylmethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.5]octane-8-sulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

4-(4-Methylsulfamoyl-4,7-diaza-spiro[2.5]oct-7-yl)-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid tert-butyl ester (intermediate 4) (0.71 mmol) was dissolved in dry DMF (0.5 mL) and added Cs2CO3 (1.42 mmol) and tert-butyl 3-(bromomethyl)pyrrolidine-1-carboxylate (0.85 mmol). Stirred at 45° C. for 16 h and then added H2O (2 mL). Extracted with EtOAc (3×2 mL) and the combined organic phases were concentrated in vacuo. The residual oil was treated with a mixture of 1,1,1,3,3,3-hexafluoro-2-propanol: 2,2,2-trifluoroethanol (3:1, 4 mL) at 150° C. for 2 h. The crude reaction mixture was concentrated on celite in vacuo and purified by standard column chromatography using methanol in DCM as eluent. The obtained compound was recrystallized in methanol:EtOAc affording the title compound as solid.

Workup

  1. extractionExtracted with EtOAc (3×2 mL)
  2. concentrationthe combined organic phases were concentrated in vacuo
  3. additionThe residual oil was treated with a mixture of 1,1,1,3,3,3-hexafluoro-2-propanol: 2,2,2-trifluoroethanol (3:1, 4 mL) at 150° C. for 2 h
  4. customThe crude reaction mixture
  5. concentrationwas concentrated on celite in vacuo
  6. custompurified by standard column chromatography
  7. customThe obtained compound was recrystallized in methanol

Sources & evidence

ORD record
ord-dec5456a0c0d4c5b896dc58d3aef7ac7
Source dataset
uspto-grants-2016_01
Patent number
US09233964B2

Reaction notes

Loading…