Thiourea → 2-(6-Fluoro-1H-benzo[d]imidazol-1-yl)-9-((R)-8-fluorochroman-4-yl)-7H-purine-8(9H)-thione

HRID 605873Notes

Reaction equation

HRID 605873 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C:10]3[N:15]=[C:14]([NH:16][C@H:17]4[C:26]5[C:21](=[C:22]([F:27])[CH:23]=[CH:24][CH:25]=5)[O:20][CH2:19][CH2:18]4)[C:13]([NH2:28])=[CH:12][N:11]=3)[C:6]=2[CH:29]=1.N[C:31](N)=[S:32]>C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C:10]3[N:15]=[C:14]4[C:13]([NH:28][C:31](=[S:32])[N:16]4[C@H:17]4[C:26]5[C:21](=[C:22]([F:27])[CH:23]=[CH:24][CH:25]=5)[O:20][CH2:19][CH2:18]4)=[CH:12][N:11]=3)[C:6]=2[CH:29]=1

Participants

4

Reactant 2

HCID 2723790ThioureaHCID 597049222-(6-fluoro-1H-benzo[d]imidazol-1-yl)N4-((R)-8-fluorochroman-4-yl)pyrimidine-4,5-diamine

Product 1

HCID 597048822-(6-Fluoro-1H-benzo[d]imidazol-1-yl)-9-((R)-8-fluorochroman-4-yl)-7H-purine-8(9H)-thioneYield 14.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
200 °C

Procedure

In a microwave vial, to the solution of 50 mg (0.13 mmol) 2-(6-fluoro-1H-benzo[d]imidazol-1-yl)N4—((R)-8-fluorochroman-4-yl)pyrimidine-4,5-diamine (known compound, e.g. WO 2006/108103) in 0.75 mL anhydrous acetonitrile was added 24 mg (0.32 mmol) thiourea. The vial was capped and the mixture was heated in an Emrys Optimizer microwave at 200° C. for 30 minutes. The resulting red dark suspension was concentrated in vacuo, and partitioned between water and EtOAc. Extract this aqueous phase with EtOAc three more times, and the combined organic layer was concentrated in vacuo, and purified by silica gel column chromatography eluting with DCM and MeOH to yield 8 mg (14%) the titled compound as a pale yellow solid. (Note: On similar diamines, cyclization with 1,1′-thiocarbonyl-diimidazole at 0° C., then slowly warm up to room temperature was found to give improved yields.)

Workup

  1. customThe vial was capped
  2. concentrationThe resulting red dark suspension was concentrated in vacuo
  3. custompartitioned between water and EtOAc
  4. extractionExtract this aqueous phase with EtOAc three more times
  5. concentrationthe combined organic layer was concentrated in vacuo
  6. custompurified by silica gel column chromatography
  7. washeluting with DCM and MeOH

Sources & evidence

ORD record
ord-51b9aa0516ea4ed086db197d0f41db12
Source dataset
uspto-grants-2011_03
Patent number
US07915268B2

Reaction notes

Loading…