Hydrochloric Acid → HCID 178508370, compound

HRID 389595Notes

Reaction equation

HRID 389595 reaction equation
C(OC([N:8](C(OC(C)(C)C)=O)[C:9]1[N:10]=[CH:11][C:12]([C:21]2[CH:22]=[N:23][N:24]([C@H:26]3[CH2:31][CH2:30][C@H:29]([O:32][Si](C(C)(C)C)(C)C)[CH2:28][CH2:27]3)[CH:25]=2)=[C:13]2[CH:17]=[C:16](B(O)O)[O:15][C:14]=12)=O)(C)(C)C.I[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1.C(=O)([O-])[O-].[K+].[K+].Cl>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.O.O1CCOCC1>[NH2:8][C:9]1[N:10]=[CH:11][C:12]([C:21]2[CH:22]=[N:23][N:24]([C@H:26]3[CH2:27][CH2:28][C@H:29]([OH:32])[CH2:30][CH2:31]3)[CH:25]=2)=[C:13]2[CH:17]=[C:16]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[O:15][C:14]=12

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 11575IodobenzeneHCID 178454343HCID 178454343, compound

Product 1

HCID 178508370HCID 178508370, compoundYield 30.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of {7-[bis(tert-butoxycarbonyl)amino]-4-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-4-yl]furo[2,3-c]pyridin-2-yl}boronic acid (15.0, 0.0228 mmol), iodobenzene (9.32 mg, 0.0456 mmol), Pd(PPh3)4 (2.64 mg, 0.0023 mmol), potassium carbonate (9.47 mg, 0.0685 mmol) and 4:1 1,4-dioxane:water (1 mL) was heated to 65° C. for 30 min. Concentrated HCl (0.0381 mL, 0.457 mmol) was added, and the solution was heated to 70° C. for 1 h. The solution was concentrated. Purification by ISCO chromatography (2 to 5% 7 N NH3/MeOH:DCM) afforded 2.6 mg (30%) of the title compound as a yellow solid. 1H NMR (400 MHz, CD3OD): δ 1.43-1.58 (m, 2 H), 1.91-2.07 (m, 2 H), 2.07-2.24 (m, 4 H), 3.70 (tt, J=10.9, 4.3 Hz, 1 H), 4.21-4.32 (m, 1 H), 7.45-7.57 (m, 3 H), 7.58 (s, 1 H), 7.82 (s, 1 H), 7.92 (s, 1 H), 8.07 (s, 1 H), 8.09 (d, J=1.5 Hz, 1 H), 8.17 (s, 1 H); MS (ESI): 375.16 [M+H]+; HPLC tR=0.75 min (TOF: polar—2 min).

Workup

  1. concentrationThe solution was concentrated
  2. customPurification by ISCO chromatography (2 to 5% 7 N NH3/MeOH:DCM)

Sources & evidence

ORD record
ord-cb1fdea702df4bb180ba0a8c44da0505
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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