N,N,N',N'-Tetramethylethylenediamine → HCID 58233781, compound

HRID 1942117Notes

Reaction equation

HRID 1942117 reaction equation
Br[C:2]1[C:7]2[O:8][C:9]3([C:15]4[C:20]([C:6]=2[CH:5]=[CH:4][CH:3]=1)=[CH:19][N:18]=[C:17]([NH2:21])[N:16]=4)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]3.[CH3:22][N:23](CCN(C)C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>CN(C=O)C.O.[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:21][C:17]1[N:16]=[C:15]2[C:9]3([O:8][C:7]4[C:6]([C:20]2=[CH:19][N:18]=1)=[CH:5][CH:4]=[CH:3][C:2]=4[C:22]#[N:23])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]3

Participants

8

Reactant 3

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58233690HCID 58233690, compound

Product 1

HCID 58233781HCID 58233781, compoundYield 337%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

A solution of 7-bromospiro[chromeno[3,4-d]pyrimidine-5,1′-cyclohexan]-3-amine (44) (0.233 g, 0.673 mmol), Zn(CN)2 (0.0474 g, 0.404 mmol), and TMEDA (0.0202 ml, 0.135 mmol), in DMF (2 mL) was degassed by bubbling nitrogen through the solution for ˜1 min before adding Pd2(dba)3 (0.0462 g, 0.0505 mmol), and Xantphos (4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene, 0.0584 g, 0.101 mmol). The mixture was heated to 160° C. for 5 min with microwave irradiation. The reaction mixture was diluted in water and extracted with 10% iPrOH/DCM (3×75 ml). The organic layer was dried with MgSO4 and concentrated in vacuo. Purification on a 40 g combiflash column [(dry loaded), eluting with 50% EtOAc:Hexane to 100% EtOAc then with 4% MeOH/36% DCM/EtOAc] afforded 3-aminospiro[chromeno[3,4-d]pyrimidine-5,1′-cyclohexane]-7-carbonitrile (47) as a white solid (0.133 g, 68%). LCMS-ESI (POS), M/Z, M+1: Found 293.0.

Workup

  1. customby bubbling nitrogen through the solution for ˜1 min
  2. extractionextracted with 10% iPrOH/DCM (3×75 ml)
  3. dry with materialThe organic layer was dried with MgSO4
  4. concentrationconcentrated in vacuo
  5. customPurification on a 40 g combiflash column [
  6. custom(dry loaded)
  7. washeluting with 50% EtOAc

Sources & evidence

ORD record
ord-cdb0d537fe6d45a4b8c01b48f4819ffb
Source dataset
uspto-grants-2013_03
Patent number
US08389533B2

Reaction notes

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