Water → HCID 54674833, compound

HRID 2095667Notes

Reaction equation

HRID 2095667 reaction equation
Br[C:2]1[C:3]([C:8]([NH2:10])=O)=[N:4][N:5]([CH3:7])[CH:6]=1.CN(C=O)C.S(Cl)(Cl)=O.[Cl:20][C:21]1[C:26]([F:27])=[CH:25][CH:24]=[C:23]([O:28][CH3:29])[C:22]=1[C@H:30]([C:32]1[C:40]2[C:35](=[N:36][CH:37]=[C:38](B3OC(C)(C)C(C)(C)O3)[CH:39]=2)[NH:34][CH:33]=1)[CH3:31].C([O-])([O-])=O.[K+].[K+].O>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O1CCOCC1>[Cl:20][C:21]1[C:26]([F:27])=[CH:25][CH:24]=[C:23]([O:28][CH3:29])[C:22]=1[C@H:30]([C:32]1[C:40]2[C:35](=[N:36][CH:37]=[C:38]([C:2]3[C:3]([C:8]#[N:10])=[N:4][N:5]([CH3:7])[CH:6]=3)[CH:39]=2)[NH:34][CH:33]=1)[CH3:31]

Participants

9

Reactant 6

HCID 962WaterHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 604541HCID 604541, compoundHCID 670040713-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 54674833HCID 54674833, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-bromo-1-methyl-1H-pyrazole-3-carboxamide (10.0 mg, 0.0490 mmol) in DMF (2 mL, 20 mmol) was added thionyl chloride (0.1 mL, 1 mmol) at 0° C., and the mixture was allowed to warm to rt. The material was extracted with EtOAc, and washed with sat. NaHCO3 (3×). The organic layer was concentrated in vacuo. 3-[(S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (10.0 mg, 0.0232 mmol), (1,1′bis-(diphenylphosphino)-ferrocene) palladium dichloride (1.79 mg, 0.00245 mmol), K2CO3 (10.0 mg, 0.0724 mmol) and 4:1 dioxane:H2O (1 mL, 10 mmol) were added, and the mixture was heated in a microwave reactor at 100° C. for 30 min. The solution was used directly for HPLC purification, and the fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.80 (d, J=7.3 Hz, 3H), 3.72 (br. s., 3H), 4.00 (s, 3H), 5.15 (q, J=6.7 Hz, 1H), 6.90 (dd, J=9.1, 4.3 Hz, 1H), 7.05 (t, J=8.8 Hz, 1H), 7.37 (d, J=1.3 Hz, 1H), 7.82 (s, 1H), 7.98 (s, 1H), 8.31 (d, J=2.0 Hz, 1H). MS (ES+): m/z=410.05/412.06 (100/50) [MH+]. HPLC: tR=4.08 min (polar—5 min, ZQ3).

Workup

  1. extractionThe material was extracted with EtOAc
  2. washwashed with sat. NaHCO3 (3×)
  3. concentrationThe organic layer was concentrated in vacuo
  4. temperaturethe mixture was heated in a microwave reactor at 100° C. for 30 min
  5. customThe solution was used directly for HPLC purification
  6. additionthe fractions containing the pure product
  7. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-8214cc9f091e44a68d89026a338ac381
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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