Water → HCID 57961036, compound

HRID 449079Notes

Reaction equation

HRID 449079 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([CH:18]3[CH2:21][CH2:20][CH2:19]3)[N:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[C:12]=23)=[CH:4][CH:3]=1.[S:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[CH:24]=[C:23]1B(O)O.O1CCOCC1.O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[S:22]1[C:23]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[N:9]=[C:10]([CH:18]4[CH2:21][CH2:20][CH2:19]4)[N:11]4[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[C:12]=34)=[CH:4][CH:3]=2)=[CH:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]1=2

Participants

6

Reactant 4

HCID 962WaterHCID 2359Benzo(B)Thiophene-2-Boronic AcidHCID 312751,4-DioxaneHCID 66915518HCID 66915518, compound

Product 1

HCID 57961036HCID 57961036, compoundYield 24.2%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A mixture of 1-(4-bromophenyl)-3-cyclobutylimidazo[1,5-a]pyrazin-8-ylamine (30.0 mg, 0.0874 mmol), 1-benzothiophen-2-ylboronic acid (18.7 mg, 0.105 mmol) and Pd(PPh3)4 (5 mg, 0.004 mmol) in 1,4-dioxane (2 mL, 30 mmol) and H2O (0.2 mL, 9 mmol) was degassed and refilled with nitrogen (3×). The reaction was microwaved on 300 watts, PowerMAX enabled, 100° C. for 30 min. For the workup, the reaction was concentrated in vacuo to a solid and purified by 10 g Jones Chromatography column wetted with DCM, dried loaded the product, eluted with DCM to 5% MeOH in DCM], which afford 8.4 mg (24%) of the desired product as a yellow solid. 1H NMR (400 MHz, CDCl3); 6=2.03-2.14 (m, 1H), 2.16-2.27 (m, 1H), 2.48-2.59 (m, 2H), 2.61-2.74 (m, 2H); 3.78-3.89 (m, 1H), 6.93 (d, J=5.56 Hz, 1H), 7.14 (d, J=5.56 Hz, 1H), 7.33-7.43 (m, 2H), 7.66 (s, 1H), 7.74 (d, J=8.59 Hz, 2H), 7.80-7.92 (m, 4H). HPLC: tR=2.71 min. (Open Lynx polar—5 min.). MS (ES+): m/z 379.80/380.91 (100/60) [MH+].

Workup

  1. customwas degassed
  2. additionrefilled with nitrogen (3×)
  3. customThe reaction was microwaved on 300 watts, PowerMAX
  4. concentrationFor the workup, the reaction was concentrated in vacuo to a solid
  5. custompurified by 10 g Jones Chromatography column
  6. customdried
  7. washeluted with DCM to 5% MeOH in DCM], which

Sources & evidence

ORD record
ord-d614be7a3d1d46378aa18ce60a667a92
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

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