Trimethylsilyl isocyanate → HCID 21066310, compound

HRID 1373442Notes

Reaction equation

HRID 1373442 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]2[C:10]([NH:11][CH2:12][CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[CH:9][C:8]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])=[N:7][C:6]=12.C[Si]([N:30]=[C:31]=[O:32])(C)C>ClCCl>[Br:1][C:2]1[CH:3]=[N:4][N:5]2[C:10]([NH:11][CH2:12][CH:13]3[CH2:14][CH2:15][N:16]([C:31]([NH2:30])=[O:32])[CH2:17][CH2:18]3)=[CH:9][C:8]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])=[N:7][C:6]=12

Participants

4

Reactant 2

HCID 70696Trimethylsilyl isocyanateHCID 21066948HCID 21066948, compound

Product 1

HCID 21066310HCID 21066310, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

[3-Bromo-5-(2-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]piperidin-4-ylmethylamine (57 mg, 0.136 mmoles) (prepared as described in Example 460, Step B above) was dissolved in anhydrous dichloromethane (1.2 mL) and trimethylsilylisocyanate (0.091 mL, 0.679 mmoles) was added. The mixture was stirred at 25° C. for 2.5h. The mixture was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate. The organic layer was dried (MgSO4), filtered and evaporated to dryness. The residue was chromatographed on a silica gel column (30×2.5 cm) using 3% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give 4-{[3-bromo-5-(2-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-ylamino]methyl}piperidine-1-carboxylic acid amide (53.7 mg, 86%): FABMS: m/z 463.1 (MH+); HRFABMS: m/z 463.0647 (MH+). Calcd. for C19H21N6OBrCl: m/z 463.0649; δH (d6-DMSO) 1.09 (2H, m, CH2), 1.63 (2H, m, CH2), 1.87 (1H, m, CH), 2.60 (2H, m, CH2), 3.53 (2H, bm, CONH2), 3.91 (2H, d, CH2), 6.52 (1H, s, H6), 7.50 (2H, m, Ar—H), 7.62 (2H, m, Ar—H), 8.33 (1H, s, H2) and 8.52 ppm (1H, m, NH); δC (d6-DMSO) CH2: 30.1, 30.1, 44.2, 44.2, 47.7; CH: 36.4, 88.2, 128.1, 130.7, 131.4, 132.1, 147.9; C: 82.1, 132.1, 139.4, 145.7, 147.9, 158.1, 158.8.

Workup

  1. washwashed with saturated aqueous sodium bicarbonate
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customThe residue was chromatographed on a silica gel column (30×2.5 cm)

Sources & evidence

ORD record
ord-02532e46863e41259cdbd24af1f4cf07
Source dataset
uspto-grants-2007_01
Patent number
US07161003B1

Reaction notes

Loading…