Water → (1S,6R)-tert-butyl 8-(6-methyl-2-(1H-1,2,3-triazol-1-yl)nicotinoyl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylate

HRID 2174997Notes

Reaction equation

HRID 2174997 reaction equation
[C@H:1]12[NH:8][CH2:7][C@H:6]1[CH2:5][CH2:4][N:3]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:2]2.[CH3:16][C:17]1[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[C:19]([N:26]2[CH:30]=[CH:29][N:28]=[N:27]2)[N:18]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.O>C(Cl)Cl>[CH3:16][C:17]1[CH:25]=[CH:24][C:20]([C:21]([N:8]2[C@H:1]3[C@H:6]([CH2:5][CH2:4][N:3]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:2]3)[CH2:7]2)=[O:22])=[C:19]([N:26]2[CH:30]=[CH:29][N:28]=[N:27]2)[N:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 16099093(1S,6R)-3-Boc-3,8-diazabicyclo[4.2.0]octaneHCID 670866896-methyl-2-(1H-1,2,3-triazol-1-yl)nicotinic acid

Product 1

HCID 67086586(1S,6R)-tert-butyl 8-(6-methyl-2-(1H-1,2,3-triazol-1-yl)nicotinoyl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylateYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of Intermediate 24 (570 mg, 2.69 mmol), 6-methyl-2-(1H-1,2,3-triazol-1-yl)nicotinic acid (603 mg, 2.95 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (1200 mg, 2.69 mmol) in DCM (15 mL) was added TEA (1.1 mL, 8.06 mmol). The resulting mixture was stirred for 5 h at ambient temperature at which time water (30 mL) was added. The aqueous layer was extracted with DCM (15 mL) three times. The organic layers were combined, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude residue was purified by FCC (SiO2, ethyl acetate/hexanes, 0-40%) to yield (1S,6R)-tert-butyl 8-(6-methyl-2-(1H-1,2,3-triazol-1-yl)nicotinoyl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylate (1.05 g, 98%). MS (ESI) mass calcd. for C20H26N6O3, 398.2; m/z found, 399.1 [M+H]+. 1H NMR (500 MHz, CDCl3): 8.48-8.38 (m, 1H), 7.82-7.79 (m, 1H), 7.77-7.64 (m, 1H), 7.33-7.23 (m, 1H), 4.53-4.27 (m, 2H), 4.06-3.89 (m, 1H), 3.80-3.36 (m, 4H), 3.01-2.90 (m, 1H), 2.62-2.58 (m, 3H), 2.03-1.76 (m, 2H), 1.53-1.42 (m, 9H).

Workup

  1. additionwas added
  2. extractionThe aqueous layer was extracted with DCM (15 mL) three times
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified by FCC (SiO2, ethyl acetate/hexanes, 0-40%)

Sources & evidence

ORD record
ord-194da45b101249129dbd5648b074f325
Source dataset
uspto-grants-2015_06
Patent number
US09062044B2

Reaction notes

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