Triethylamine → Pf-5190457

HRID 2205093Notes

Reaction equation

HRID 2205093 reaction equation
Cl.Cl.[CH3:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[C@H:15]([N:19]2[CH2:22][C:21]4([CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)[CH2:20]2)[CH2:14][CH2:13]3)[CH:5]=1.C(N(CC)CC)C.Cl.[CH3:36][C:37]1[S:41][C:40]2=[N:42][C:43]([CH2:45][C:46](O)=[O:47])=[CH:44][N:39]2[CH:38]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C=O)C>[CH3:36][C:37]1[S:41][C:40]2=[N:42][C:43]([CH2:45][C:46]([N:25]3[CH2:26][CH2:27][C:21]4([CH2:22][N:19]([C@H:15]5[C:16]6[C:12](=[CH:11][C:10]([C:6]7[CH:5]=[C:4]([CH3:3])[N:9]=[CH:8][N:7]=7)=[CH:18][CH:17]=6)[CH2:13][CH2:14]5)[CH2:20]4)[CH2:23][CH2:24]3)=[O:47])=[CH:44][N:39]2[CH:38]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67405889HCID 67405889, compoundHCID 674062952-[(R)-5-(6-methyl-pyrimidin-4-yl)-indan-1-yl]-2,7-diaza-spiro[3.5]nonane dihydrochloride

Product 1

HCID 58438464Pf-5190457

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a suspension of 2-[(R)-5-(6-methyl-pyrimidin-4-yl)-indan-1-yl]-2,7-diaza-spiro[3.5]nonane dihydrochloride (540 mg, 1.22 mmol) in 10 mL of dichloromethane was added triethylamine (492 mg, 4.90 mmol). Once the mixture became a homogenous solution, it was added to a solution of 2-(2-methylimidazo[2,1-b]thiazol-6-yl)acetic acid hydrochloride (251 mg, 1.28 mmol) in 3 mL of dichloromethane. The mixture was stirred for 5 minutes and HBTU (462 mg, 1.22 mmol) in 2 mL of DMF was added. The reaction was stirred at room temperature for 1.5 hours. The reaction was quenched by the addition of 10 mL of NaHCO3 and was diluted with 50 mL of dichloromethane. The organic layer was washed with saturated brine, dried over Na2SO4, filtered and the filtrate was concentrated. The residue was dissolved in 5 mL of CH3CN and the solution was heated to 100° C. for 1 hour with stirring. The mixture was cooled to room temperature and the resulting solids were vacuum filtered to afford the desired product as an off white powder (428 mg, 69%). MS (ES+) 513.5 (M+H)+. 1H NMR (CD3OD) δ 1.70-1.74 (m, 4H), 1.88-1.96 (m, 1H), 2.27-2.34 (m, 2H), 2.40 (s, 3H), 2.58 (s, 3H), 2.86-2.97 (m, 1H), 3.11-3.15 (m, 1H), 3.31-3.34 (m, 3H), 3.52-3.55 (m, 4H), 3.78 (s, 2H), 4.05-4.09 (m, 1H), 7.33 (s, 2H), 7.55 (d, 1H), 7.78-7.79 (m, 1H), 7.94-8.03 (m, 2H), 8.93 (s, 1H). [α]D20=+45.3 deg (c=2.5 mg/mL, MeOH).

Workup

  1. stirringThe reaction was stirred at room temperature for 1.5 hours
  2. customThe reaction was quenched by the addition of 10 mL of NaHCO3
  3. additionwas diluted with 50 mL of dichloromethane
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. dissolutionThe residue was dissolved in 5 mL of CH3CN
  9. stirringwith stirring
  10. temperatureThe mixture was cooled to room temperature
  11. filtrationfiltered

Sources & evidence

ORD record
ord-b7c87b645d314e21b925e9b798d7f512
Source dataset
uspto-grants-2016_06
Patent number
US09370516B2

Reaction notes

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