Cyclopropylboronic acid → HCID 57546172, compound

HRID 913824Notes

Reaction equation

HRID 913824 reaction equation
Br[C:2]1[N:3]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[N:4]=[C:5]2[C:10]=1[CH:9]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:7]=[C:6]2[CH2:15][O:16][CH2:17][C:18]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1.[CH:45]1(B(O)O)[CH2:47][CH2:46]1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:45]1([C:2]2[N:3]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[N:4]=[C:5]3[C:10]=2[CH:9]=[C:8]([C:11]([F:12])([F:14])[F:13])[CH:7]=[C:6]3[CH2:15][O:16][CH2:17][C:18]2([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH2:20][CH2:19]2)[CH2:47][CH2:46]1

Participants

4

Reactant 2

HCID 2760897Cyclopropylboronic acidHCID 57546071HCID 57546071, compound

Product 1

HCID 57546172HCID 57546172, compound

Reagents, catalysts & solvents 1

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

tert-Butyl 4-(((3-bromo-5-(trifluoromethyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (36 mg, 0.05 mmol), cyclopropylboronic acid (13 mg, 0.16 mmol), and tetrakis(triphenylphosphine) palladium(0) (6 mg, 0.005 mmol) were combined in dry tetrahydrofran (2 mL) in a microwave tube and sealed. The mixture was flushed with nitrogen then 180 μL of a 1 N potassium hydroxide aqueous solution was introduced. The mixture was heated at 100° C. for 1 h via microwave. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, washed with water (2×), then brine (2×), dried over sodium sulfate, and concentrated. Flash chromatography on silica gel (15% ethyl acetate/hexanes) gave 18 mg (53%). 1H-NMR (CDCl3, 500 MHz) δ 7.99 (s, 1H), 7.37 (s, 1H), 7.15-7.21 (m, 5H), 5.30 (s, 2H), 4.68 (s, 2H), 3.68 (m, 2H), 3.43 (s, 2H), 3.35-3.38 (m, 2H), 2.98-3.02 (m, 2H), 2.10-2.19 (m, 3H), 1.74-1.79 (m, 2H), 1.41 (s, 9H), 1.03-1.06 (m, 4H), 0.73-0.76 (m, 2H), 0.11 (s, 9H). Mass spec.: 660.31 (MH)+.

Workup

  1. customsealed
  2. customThe mixture was flushed with nitrogen
  3. addition180 μL of a 1 N potassium hydroxide aqueous solution was introduced
  4. temperatureAfter cooling to room temperature
  5. additionthe reaction mixture was diluted with ethyl acetate
  6. washwashed with water (2×)
  7. dry with materialbrine (2×), dried over sodium sulfate
  8. concentrationconcentrated
  9. customFlash chromatography on silica gel (15% ethyl acetate/hexanes) gave 18 mg (53%)

Sources & evidence

ORD record
ord-8d152a8a2dc94e35917b11f9646fdb08
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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