Water → HCID 54674989, compound

HRID 2095662Notes

Reaction equation

HRID 2095662 reaction equation
Br[C:2]1[C:3]([CH3:11])=[N:4][N:5]([CH3:10])[C:6]=1[C:7]([OH:9])=O.[NH4+].[Cl-].C[N:15](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.CN(C=O)C.[Cl:50][C:51]1[C:56]([F:57])=[CH:55][CH:54]=[C:53]([O:58][CH3:59])[C:52]=1[C@H:60]([C:62]1[C:70]2[C:65](=[N:66][CH:67]=[C:68](B3OC(C)(C)C(C)(C)O3)[CH:69]=2)[NH:64][CH:63]=1)[CH3:61].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:50][C:51]1[C:56]([F:57])=[CH:55][CH:54]=[C:53]([O:58][CH3:59])[C:52]=1[C@H:60]([C:62]1[C:70]2[C:65](=[N:66][CH:67]=[C:68]([C:2]3[C:3]([CH3:11])=[N:4][N:5]([CH3:10])[C:6]=3[C:7]([NH2:15])=[O:9])[CH:69]=2)[NH:64][CH:63]=1)[CH3:61]

Participants

11

Reactant 8

HCID 962WaterHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27798334-bromo-1,3-dimethyl-1H-pyrazole-5-carboxylic acidHCID 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 54674989HCID 54674989, compound

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 4-bromo-1,3-dimethyl-1H-pyrazole-5-carboxylic acid (20.0 mg, 0.0913 mmol), NH4Cl (48.8 mg, 0.913 mmol), TBTU (58.6 mg, 0.183 mmol), DIPEA (0.159 mL, 0.913 mmol) and DMF (2 mL, 20 mmol) was stirred at rt for 10 min. The material was extracted with EtOAc, and washed with sat. NaHCO3 (3×) to remove carboxylic acid starting material. 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 (15.0 mg, 0.0348 mmol), (1,1′bis-(diphenylphosphino)-ferrocene) palladium dichloride (3.34 mg, 0.00456 mmol), K2CO3 (18.9 mg, 0.137 mmol) and 4:1 dioxane:H2O (1 mL, 10 mmol) were added, and the mixture was heated to 95° 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), 2.04 (s, 3H), 3.66 (br. s., 3H), 3.95 (s, 3H), 5.11 (q, J=6.8 Hz, 1H), 6.90 (dd, J=9.0, 4.2 Hz, 1H), 7.08 (t, J=8.8 Hz, 1H), 7.37 (d, J=1.3 Hz, 1H), 7.45 (s, 1H), 8.07 (br. s., 1H). MS (ES+): m/z=442.14/444.14 (100/50) [MH+]. HPLC: tR=1.37 min (polar—3 min, UPLC-ACQUITY).

Workup

  1. extractionThe material was extracted with EtOAc
  2. washwashed with sat. NaHCO3 (3×)
  3. customto remove carboxylic acid starting material
  4. concentrationThe organic layer was concentrated in vacuo
  5. temperaturethe mixture was heated to 95° C. for 30 min
  6. customThe solution was used directly for HPLC purification
  7. additionthe fractions containing the pure product
  8. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-8e78ff9f52a74ddba6c4ae939067f1c8
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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