7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d][1,2,3]thiadiazole → HCID 178421898, compound

HRID 389587Notes

Reaction equation

HRID 389587 reaction equation
[Si]([O:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[CH:19]=[C:18]([C:20]3[CH:25]=[N:24][C:23]([NH2:26])=[C:22]4[O:27][C:28](Cl)=[C:29]([CH3:30])[C:21]=34)[CH:17]=[N:16]2)[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.CC1(C)C(C)(C)OB([C:40]2[C:48]3[S:47][N:46]=[N:45][C:44]=3[CH:43]=[CH:42][CH:41]=2)O1>O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].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>[NH2:26][C:23]1[N:24]=[CH:25][C:20]([C:18]2[CH:17]=[N:16][N:15]([C@H:12]3[CH2:11][CH2:10][C@H:9]([OH:8])[CH2:14][CH2:13]3)[CH:19]=2)=[C:21]2[C:29]([CH3:30])=[C:28]([C:40]3[C:48]4[S:47][N:46]=[N:45][C:44]=4[CH:43]=[CH:42][CH:41]=3)[O:27][C:22]=12

Participants

6

Reactant 2

HCID 667606827-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d][1,2,3]thiadiazoleHCID 178427971HCID 178427971, compound

Product 1

HCID 178421898HCID 178421898, compoundYield 27.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-4-yl]-2-chloro-3-methylfuro[2,3-c]pyridin-7-amine (20 mg, 0.043 mmol), 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3-benzothiadiazole (12.5 mg, 0.0477 mmol), and Pd(PPh3)4 (5.0 mg, 0.0043 mmol) in 1,4-dioxane (0.2 mL) and 1.0 M aqueous sodium carbonate (0.2 mL) was heated to 120° C. in a microwave for 60 min. The organic phase was separated, treated with 12 M aqueous HCl (0.071 mL) at 40° C. for 1 h, and then concentrated. Purification by ISCO chromatography (0 to 15% 7 N NH3/MeOH:DCM) followed by trituration from DCM:hexanes (˜5 mL, 1:1) and filtration afforded 5.3 mg (27%) of the title compound as an orange solid. 1H NMR (400 MHz, DMSO-d6): δ 8.83 (d, J=7.8 Hz, 1 H), 8.19 (d, J=6.8 Hz, 1 H), 7.90-8.03 (m, 2 H), 7.67 (s, 1 H), 7.58 (d, J=0.5 Hz, 1 H), 6.38 (s, 2 H), 4.67 (d, J=4.3 Hz, 1 H), 4.09-4.27 (m, 1 H), 3.42-3.60 (m, 1 H), 2.27 (s, 3 H), 2.06 (d, J=12.1 Hz, 2 H), 1.90-1.98 (m, 2 H), 1.77-1.90 (m, 2 H), 1.28-1.48 (m, 2 H); MS (ESI): 446.85, 448.96 [M+H]+; HPLC tR=2.51 min (ZQ3: polar—4 min).

Workup

  1. customThe organic phase was separated
  2. additiontreated with 12 M aqueous HCl (0.071 mL) at 40° C. for 1 h
  3. concentrationconcentrated
  4. customPurification by ISCO chromatography (0 to 15% 7 N NH3/MeOH:DCM)
  5. filtrationhexanes (˜5 mL, 1:1) and filtration

Sources & evidence

ORD record
ord-20f0deb43d1d4ce785f0760d6f6b422e
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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