Hydrochloric Acid → HCID 178508369, compound

HRID 389515Notes

Reaction equation

HRID 389515 reaction equation
C([Si](C)(C)[O:6][CH:7]1[CH2:12][CH2:11][CH:10]([N:13]2[CH:17]=[C:16]([C:18]3[CH:23]=[N:22][C:21]([NH2:24])=[C:20]4[O:25][C:26](Cl)=[CH:27][C:19]=34)[CH:15]=[N:14]2)[CH2:9][CH2:8]1)(C)(C)C.CC1(C)C(C)(C)OB([C:39]2[C:47]3[S:46][N:45]=[N:44][C:43]=3[CH:42]=[CH:41][CH:40]=2)O1.C(=O)([O-])[O-].[K+].[K+].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.CO.O.O1CCOCC1>[NH2:24][C:21]1[N:22]=[CH:23][C:18]([C:16]2[CH:15]=[N:14][N:13]([C@H:10]3[CH2:9][CH2:8][C@H:7]([OH:6])[CH2:12][CH2:11]3)[CH:17]=2)=[C:19]2[CH:27]=[C:26]([C:39]3[C:47]4[S:46][N:45]=[N:44][C:43]=4[CH:42]=[CH:41][CH:40]=3)[O:25][C:20]=12

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 667601224-{1-[4-(tert-butyldimethyl-silanyloxy)-cyclohexyl]-1H-pyrazol-4-yl}-2-chlorofuro[2,3-c]pyridin-7-ylamineHCID 667606827-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d][1,2,3]thiadiazole

Product 1

HCID 178508369HCID 178508369, compoundYield 50%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 4-{1-[4-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-1H-pyrazol-4-yl}-2-chloro-furo[2,3-c]pyridin-7-ylamine (179 mg, 0.400 mmol), 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3-benzothiadiazole (105.0 mg, 0.4006 mmol), Pd(PPh3)4 (46.3 mg, 0.0400 mmol), potassium carbonate (166 mg, 1.20 mmol) and 4:1 1,4-dioxane:water (6 mL) was heated in a microwave reactor at 110° C. for 1 h. Aqueous 12 N hydrochloric acid (0.5 mL, 6 mmol) and methanol (2 mL) were added, and the solution was heated to 30° C. for 30 min. The organic solvent was removed in vacuo, and the material was extracted with DCM and saturated aqueous sodium bicarbonate (2×). The organic layer was purified by column chromatography (1 to 3% 7 N ammonia/methanol:DCM), followed by trituration from methanol (5 mL) and filtration to afford 80 mg (50%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 1.31-1.46 (m, 2 H), 1.82-2.02 (m, 4 H), 2.04-2.15 (m, 2 H), 3.48-3.61 (m, 1 H), 4.14-4.25 (m, 1 H), 4.71 (d, J=4.5 Hz, 1 H), 6.42 (s, 2 H), 7.94-8.03 (m, 3 H), 8.06 (s, 1 H), 8.26 (s, 1 H), 8.65 (dd, J=7.5, 0.6 Hz, 1 H), 8.81-8.89 (m, 1 H); MS (ESI): 433.14 [M+H]+; HPLC tR=1.18 min (TOF: polar—3 min).

Workup

  1. customThe organic solvent was removed in vacuo
  2. extractionthe material was extracted with DCM and saturated aqueous sodium bicarbonate (2×)
  3. customThe organic layer was purified by column chromatography (1 to 3% 7 N ammonia/methanol:DCM)
  4. filtrationfollowed by trituration from methanol (5 mL) and filtration

Sources & evidence

ORD record
ord-103bb54fc23644ddbb5126af6b490885
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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