Triethylamine → HCID 131736611, compound

HRID 1480535Notes

Reaction equation

HRID 1480535 reaction equation
[CH3:1][O:2][C:3]1[CH:27]=[CH:26][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][N:18]=3)=[O:16])[CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1.[F:28][C:29]([F:45])([F:44])[CH:30]1[CH:35]([NH2:36])[CH2:34][CH2:33][N:32]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:31]1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([CH:9]2[CH2:10][CH2:11][N:12]([C:15]([C:17]3[CH:25]=[CH:24][C:20]([C:21]([NH:36][C@H:35]4[CH2:34][CH2:33][N:32]([C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])[CH2:31][C@H:30]4[C:29]([F:28])([F:44])[F:45])=[O:22])=[CH:19][N:18]=3)=[O:16])[CH2:13][CH2:14]2)=[O:8])=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21054727tert-Butyl 4-amino-3-(trifluoromethyl)piperidine-1-carboxylateHCID 58073418HCID 58073418, compound

Product 1

HCID 131736611HCID 131736611, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 6-(4-(4-methoxybenzoyl)piperidine-1-carbonyl)nicotinic acid (0.094 g, 0.257 mmol, 1.0 eq), and 3-trifluoromethyl-4-amino-1-Boc-piperidine (0.257 mmol, 1.0 eq) was added dimethylformamide (2.5 mL) and triethylamine (0.054 mL, 0.386 mmol, 1.5 eq). HATU (0.107 g, 0.283 mmol, 1.1 eq) was added and the reaction was stirred at room temperature for 14 hours and partitioned between EtOAc (120 mL) and NaHCO3-water (1:1, 120 mL). The organics were further washed with brine (100 mL), water (100 mL) and brine (100 mL), dried (Na2SO4) and concentrated under reduced pressure. MPLC (0→10% MeOH—CH2Cl2) yielded the coupled product (0.104 g, 68%) as a colourless oil; 1H nmr (CDCl3) δ 8.90 (1H, br s, pyH-6), 8.08 (1H, br d, J 7.0 Hz, pyH-4), 7.92 (2H, d, J 9.0 Hz, 2H of C6H4OMe), 7.50 (2H, m, pyH-3, NH), 6.94 (2H, d, J 9.0 Hz, 2H of C6H4OMe), 4.61 (2H, m, 1H of pipH-2, H-4, H-6, 1H of BzpipH-2, H-6), 3.86 (3H, s, OCH3), 3.86-3.74 (2H, m, 1H of pipH-2, H-4, H-6, 1H of BzpipH-2, H-6), 3.52 (1H, m, BzpipH-4), 3.52-3.38 (2H, m, 2H of pipH-2, H-4, H-6), 3.26-3.04 (1H, m, 1H of pipH-2, H-3, H-4, H-6), 3.22 (1H, m, 1H of BzpipH-2, H-6), 3.12 (1H, t, J 11.5 Hz, 1H of BzpipH-2, H-6), 2.76 (1H, m, 1H of pipH-2, H-3, H-4, H-6), 2.00 (1H, m, 1H of BzpipH-3, H-5), 1.90-1.65 (5H, m, pipH-5, 3H of BzpipH-3, H-5), 1.45 (9H, s, C(CH3)3); 19F nmr (CDCl3) δ −62.7; m/z 619 [M+H]+.

Workup

  1. custompartitioned between EtOAc (120 mL) and NaHCO3-water (1:1, 120 mL)
  2. washThe organics were further washed with brine (100 mL), water (100 mL) and brine (100 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2cd96d2befb6452aac182e2895ff92d9
Source dataset
uspto-grants-2016_08
Patent number
US09409884B2

Reaction notes

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