Hydrochloric Acid → HCID 178491836, compound

HRID 2095676Notes

Reaction equation

HRID 2095676 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C@@H:11]([C:13]3[C:18]([O:19][CH3:20])=[CH:17][CH:16]=[C:15]([F:21])[C:14]=3[Cl:22])[CH3:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[Si]([O:30][C@@H:31]1[CH2:36][CH2:35][C@H:34]([N:37]2[C:41]([CH3:42])=[C:40](B3OC(C)(C)C(C)(C)O3)[CH:39]=[N:38]2)[CH2:33][CH2:32]1)(C(C)(C)C)(C)C.C([O-])([O-])=O.[K+].[K+].O.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.O1CCOCC1>[Cl:22][C:14]1[C:15]([F:21])=[CH:16][CH:17]=[C:18]([O:19][CH3:20])[C:13]=1[C@H:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:40]3[CH:39]=[N:38][N:37]([C@@H:34]4[CH2:35][CH2:36][C@H:31]([OH:30])[CH2:32][CH2:33]4)[C:41]=3[CH3:42])[CH:3]=2)[NH:8][CH:9]=1)[CH3:12]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 962Water2×HCID 11430Potassium CarbonateHCID 670045375-Bromo-3-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridineHCID 178421687HCID 178421687, compound

Product 1

HCID 178491836HCID 178491836, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5-bromo-3-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine (200.0 mg, 0.5213 mmol), 1-(cis-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (328.8 mg, 0.7820 mmol), Pd(PPh3)4 (30.12 mg, 0.02606 mmol), K2CO3 (216.1 mg, 1.564 mmol) and 4:1 dioxane:H2O (10 mL, 100 mmol) was heated to 95° C. for 2 h. The solution was cooled to rt, and 12 M of HCl in H2O (0.4344 mL, 5.213 mmol) was added. The material was concentrated in vacuo, and extracted with DCM and sat. NaHCO3. The organic layer was dry-loaded onto silica gel and purified via column chromatography, eluting with 2-4% (7N NH3 in MeOH)/DCM. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a light yellow solid. 1H NMR (400 MHz, CD3OD): δ=1.69-1.80 (m, 4H), 1.82 (d, J=7.3 Hz, 3H), 1.94-2.05 (m, 2H), 2.25 (s, 3H), 2.32-2.46 (m, 2H), 3.67 (br. s., 3H), 4.02-4.08 (m, 1H), 4.17-4.27 (m, 1H), 5.08-5.17 (m, 1H), 6.91 (dd, J=9.1, 4.3 Hz, 1H), 7.10 (t, J=8.8 Hz, 1H), 7.36 (d, J=1.3 Hz, 1H), 7.38-7.45 (m, 1H), 7.47 (s, 1H), 8.12 (d, J=2.0 Hz, 1H). MS (ES+): m/z=483.16/485.18 (100/50) [MH+]. HPLC: tR=1.46 min (polar—3 min, UPLC-ACQUITY).

Workup

  1. concentrationThe material was concentrated in vacuo
  2. extractionextracted with DCM and sat. NaHCO3
  3. custompurified via column chromatography
  4. washeluting with 2-4% (7N NH3 in MeOH)/DCM
  5. additionThe fractions containing the pure product
  6. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-f3862c631a9b49b39d7b8025625a03c6
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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