Dichloromethane → [5-(1H-Pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-ylmethyl]-carbamic acid tert-butyl ester

HRID 1625427Notes

Reaction equation

HRID 1625427 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][CH2:8][C:9]1[S:10][C:11](Br)=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].C(OC([N:23]1[C:27]2=[N:28][CH:29]=[CH:30][CH:31]=[C:26]2[C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24]1)=O)(C)(C)C.ClCCl.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6](=[O:15])[NH:7][CH2:8][C:9]1[S:10][C:11]([C:25]2[C:26]3[C:27](=[N:28][CH:29]=[CH:30][CH:31]=3)[NH:23][CH:24]=2)=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2779810tert-Butyl ((5-bromothiophen-2-yl)methyl)carbamateHCID 53217196tert-Butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Product 1

HCID 59362564[5-(1H-Pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-ylmethyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

Into a vial was dissolved (5-bromo-thiophen-2-ylmethyl)-carbamic acid tert-butyl ester (115 mg, 0.000394 mol; Maybridge), 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (119 mg, 0.000346 mol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (28 mg, 0.000034 mol; Strem) in 1,4-dioxane (6.0 mL, 0.077 mol; Acros). To this was added 2.0 M of sodium carbonate in water (1.5 mL). The reaction was purged with Ar and sealed. The reaction was heated at 110° C. under an atmosphere of Argon for 2 hours. The reaction was diluted with methylene chloride and washed with water. The organic layer was dried with magnesium sulfate, filtered and evaporated. The residue was taken up in DMSO and purified by preparative HPLC to yield the title compound in 33.4 mg yield (22%) as the TFA salt. MS m/z=330.15 (M+1). 1H NMR (400 MHz, CDCl3)™ ppm 13.919 (s, 1H) 8.703 (dd, J=7.9, 1.1 Hz, 1H) 8.246 (dd, J=5.7, 1.0 Hz, 1H) 7.676 (d, J=1.7 Hz, 1H) 7.464 (dd, J=7.9, 5.8 Hz, 1H) 7.111 (d, J=3.6 Hz, 1H) 6.985 (d, J=3.6 Hz, 1H) 4.981 (s (br), 1H) 4.508 (d, J=5.7 Hz, 2H) 1.485 (s, 9H).

Workup

  1. customThe reaction was purged with Ar
  2. customsealed
  3. additionThe reaction was diluted with methylene chloride
  4. washwashed with water
  5. dry with materialThe organic layer was dried with magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-53d7033676b64f6080220e8396edb294
Source dataset
uspto-grants-2014_07
Patent number
US08778977B2

Reaction notes

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