Acetonitrile → HCID 178429691, compound

HRID 2173917Notes

Reaction equation

HRID 2173917 reaction equation
[OH:1][CH:2]([C:22]1[C:30]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:29][C:28]([CH3:35])=[C:27]2[C:23]=1[CH:24]=[CH:25][N:26]2S(C1C=CC(C)=CC=1)(=O)=O)[C:3]1[N:7](COCC[Si](C)(C)C)[C:6]2[CH:16]=[C:17]([C:20]#[N:21])[CH:18]=[CH:19][C:5]=2[N:4]=1.OC(C1C(S(C)(=O)=O)=CC(C)=C2C=1C=CN2S(C1C=CC(C)=CC=1)(=O)=O)C1N(COCC[Si](C)(C)C)C2C=CC(C#N)=CC=2N=1.F[B-](F)(F)F.[Li+].CC#N.CCN(CCOC(C1(CCC(C)C)CCCCC1)=O)CC.[OH-].[K+]>O>[OH:1][CH:2]([C:22]1[C:30]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:29][C:28]([CH3:35])=[C:27]2[C:23]=1[CH:24]=[CH:25][NH:26]2)[C:3]1[NH:4][C:5]2[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][C:6]=2[N:7]=1

Participants

8

Reactant 6

HCID 6342AcetonitrileHCID 14797Potassium HydroxideHCID 28221IsomylamineHCID 4298216Lithium tetrafluoroborateHCID 86701456HCID 86701456, compoundHCID 86701457HCID 86701457, compound

Product 1

HCID 178429691HCID 178429691, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
70 °C

Procedure

To a mixture of (±)-2-(hydroxy(7-methyl-5-(methylsulfonyl)-1-tosyl-1H-indol-4-yl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-6-carbonitrile and (±)-2-(hydroxy(7-methyl-5-(methylsulfonyl)-1-tosyl-1H-indol-4-yl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-carbonitrile (100 mg, 0.150 mmol) was added a 1 M solution of lithium tetrafluoroborate in MeCN (3.0 mL, 3 mmol). Water (0.3 mL) was then added and the reaction heated to 70° C. overnight. The reaction mixture was cooled to room temperature, diluted with water and extracted with EtOAc. The organic extract was dried over MgSO4, filtered and concentrated. The resulting residue was dissolved in EtOH (1.3 mL) and isomylamine (0.3 mL, 2.6 mmol) and KOH (0.072 g, 1.3 mmol) were added. The mixture was then heated to 100° C. for 1 h using microwave irradiation. The mixture was then concentrated directly and purified using FCC eluting with DCM:MeOH:NH4OH 100:0:0 to 80:18:2 to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ 13.17 (br. s., 1H), 11.50 (br. s., 1H), 7.83-8.00 (m, 1H), 7.61-7.67 (m, 1H), 7.49-7.58 (m, 2H), 7.41-7.49 (m, 1H), 7.35 (q, J=2.40 Hz, 1H), 6.91 (dd, J=4.67, 7.58 Hz, 1H), 6.58 (dt, J=1.89, 3.66 Hz, 1H), 3.46 (m, 3H), 2.53 (s, 3H). HRMS calcd. for C19H16N4O3S (M+H)+ 381.1021. found 381.1013.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc
  3. extractionThe organic extract
  4. dry with materialwas dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe resulting residue was dissolved in EtOH (1.3 mL)
  8. temperatureThe mixture was then heated to 100° C. for 1 h
  9. custommicrowave irradiation
  10. concentrationThe mixture was then concentrated directly
  11. custompurified
  12. washeluting with DCM:MeOH:NH4OH 100:0:0 to 80:18:2

Sources & evidence

ORD record
ord-e37ee49ac0874f6e8d08c11ad1131871
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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