Hydrochloric Acid → HCID 57731538, compound

HRID 2234699Notes

Reaction equation

HRID 2234699 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:19]=3[NH:18][CH:17]=[CH:16]4)=[CH:9][N:8]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1.[CH3:30][O:31][C:32](=[O:56])[C:33]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[CH:35][C:34]=1[NH:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50].C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Na+].Cl>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].C(#N)C.C1COCC1>[CH3:30][O:31][C:32](=[O:56])[C:33]1[CH:38]=[C:37]([C:2]2[CH:3]=[C:4]3[C:10]([C:11]4[CH:12]=[CH:13][CH:14]=[C:15]5[C:19]=4[NH:18][CH:17]=[CH:16]5)=[CH:9][N:8]([S:20]([C:23]4[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=4)(=[O:22])=[O:21])[C:5]3=[N:6][CH:7]=2)[CH:36]=[CH:35][C:34]=1[NH:48][C:49]([O:51][C:52]([CH3:54])([CH3:53])[CH3:55])=[O:50]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 57731579HCID 57731579, compoundHCID 686921261070979-39-3

Product 1

HCID 57731538HCID 57731538, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 5-bromo-3-(1H-indol-7-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (802 mg, 1.7 mmol) and 2-tert-butoxycarbonylamino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester (641 mg, 1.7 mmol) in a 20 mL microwave reaction flask was added THF (6 mL), acetonitrile (6 mL) and sodium carbonate (6 mL, 1 N aqueous solution, 6 mmol). The mixture was purged with nitrogen for 1 minute. Dichloro[1,1′-bis(diphenylphoshino)ferrocene]palladium(II) dichloromethane adduct (122 mg, 170 μmol) was added and the purging continued for another minute. The flask was sealed and irradiated in a microwave reactor to 70° C. for 15 minutes. Saturated sodium chloride (15 mL) was added and the pH was adjusted to 7 using hydrochloric acid (1 N). The resulting mixture was extracted with ethyl acetate (10 mL×3). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel using a gradient of methanol in dichloromethane to afford 2-tert-butoxycarbonylamino-5-[3-(1H-indol-7-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoic acid methyl ester as a yellow solid (605 mg, 56% yield). MS: m/z 637 (M+H+).

Workup

  1. customin a 20 mL microwave reaction flask
  2. customThe mixture was purged with nitrogen for 1 minute
  3. customThe flask was sealed
  4. customirradiated in a microwave reactor to 70° C. for 15 minutes
  5. extractionThe resulting mixture was extracted with ethyl acetate (10 mL×3)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on silica gel using a gradient of methanol in dichloromethane

Sources & evidence

ORD record
ord-7d1a35171ae3417ab71990f0b732976c
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

Loading…