Triethylamine → 7-[(4-Cyclopropylphenyl)acetyl]-2-(5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane

HRID 1913477Notes

Reaction equation

HRID 1913477 reaction equation
C(N(CC)CC)C.Cl.Cl.[N:10]1[CH:15]=[CH:14][CH:13]=[N:12][C:11]=1[C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[CH:21]([N:25]1[CH2:28][C:27]3([CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)[CH2:26]1)[CH2:20][CH2:19]2.[CH:34]1([C:37]2[CH:42]=[CH:41][C:40]([CH2:43][C:44](O)=[O:45])=[CH:39][CH:38]=2)[CH2:36][CH2:35]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[CH:34]1([C:37]2[CH:38]=[CH:39][C:40]([CH2:43][C:44]([N:31]3[CH2:30][CH2:29][C:27]4([CH2:26][N:25]([CH:21]5[C:22]6[C:18](=[CH:17][C:16]([C:11]7[N:12]=[CH:13][CH:14]=[CH:15][N:10]=7)=[CH:24][CH:23]=6)[CH2:19][CH2:20]5)[CH2:28]4)[CH2:33][CH2:32]3)=[O:45])=[CH:41][CH:42]=2)[CH2:36][CH2:35]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 204905282-(4-Cyclopropylphenyl)acetic acidHCID 674119802-(5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane dihydrochloride

Product 1

HCID 533902757-[(4-Cyclopropylphenyl)acetyl]-2-(5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (0.1 mL) was added to a solution of 2-(5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane dihydrochloride (5-1b, 80 mg, 0.2 mmol), 4-cyclopropylphenylacetic acid (SM-1ag, 31 mg, 0.2 mmol), and HATU (93 mg, 0.24 mmol) in dichloromethane (5 mL) in a vial. The reaction was stirred at room temperature overnight and was quenched with aqueous sodium bicarbonate. The organic layer was dried over MgSO4, filtered and concentrated. The residue was chromatographed on a Combiflash ISCO purification system (Teledyne Corp., Lincoln, Nebr.) using a 12 g silica column with dichloromethane-methanol as eluant. The final product was obtained as off-white solid (89 mg, 92%). MS (APCI) 478.6 (M+H)+. 1H NMR (CDCl3) δ 0.65-0.69 (m, 3H), 0.92-0.97 (m, 2H), 1.67-1.71 (m, 2H), 1.83-1.90 (m, 2H), 2.19-2.22 (m, 1H), 2.89 (s, 1H), 3.18-3.26 (m, 5H), 3.31-3.35 (m, 2H), 3.51-3.55 (m, 2H), 3.66-3.70 (m, 3H), 4.01-4.06 (m, 1H), 7.00-7.04 (m, 2H), 7.10-7.13 (m, 2H), 7.17-7.21 (m, 1H), 7.41 (s, 1H), 8.31 (s, 2H), 8.79-8.82 (m, 2H).

Workup

  1. customwas quenched with aqueous sodium bicarbonate
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was chromatographed on a Combiflash ISCO purification system (Teledyne Corp., Lincoln, Nebr.)

Sources & evidence

ORD record
ord-6aa70af1823948848a6942427c835740
Source dataset
uspto-grants-2013_12
Patent number
US08609680B2

Reaction notes

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