4-Methoxyphenylacetic Acid → HCID 58438475, compound

HRID 1913472Notes

Reaction equation

HRID 1913472 reaction equation
Cl.Cl.[N:3]1[CH:8]=[CH:7][CH:6]=[N:5][C:4]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[C@H:14]([N:18]1[CH2:21][C:20]3([CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[CH2:19]1)[CH2:13][CH2:12]2.[CH3:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][C:36](O)=[O:37])=[CH:31][CH:30]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.C(OCC)C>[CH3:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][C:36]([N:24]2[CH2:23][CH2:22][C:20]3([CH2:19][N:18]([C@H:14]4[C:15]5[C:11](=[CH:10][C:9]([C:4]6[N:5]=[CH:6][CH:7]=[CH:8][N:3]=6)=[CH:17][CH:16]=5)[CH2:12][CH2:13]4)[CH2:21]3)[CH2:26][CH2:25]2)=[O:37])=[CH:31][CH:30]=1

Participants

7

Reactant 4

HCID 76904-Methoxyphenylacetic AcidHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67405180HCID 67405180, compound

Product 1

HCID 58438475HCID 58438475, compoundYield 82.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-[(1R)-5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane dihydrochloride (3-1e, 600 mg, 1.40 mmol), p-methoxyphenylacetic acid (232 mg, 1.40 mmol), HBTU (529 mg, 1.40 mmol) and triethylamine (1.2 mL, 8.6 mmol) in 5 mL of DMF was stirred at room temperature for 20 hours. The solvent was removed in vacuo, the residue was azeotroped with toluene and partitioned between 1N NaOH (50 mL) and ethyl acetate (50 mL). The organic layer was washed with brine, dried (Na2SO4) and concentrated. The crude product was purified on an Analogix (Analogix Inc., Burlington, Wis.) 24 g silica column (1-15% MeOH in DCM in 30 minutes) to give the product as a light foam. This solid was stirred with diethyl ether (80 mL) for 18 h and filtered to give the title compound as a light grey solid (540 mg, 82%). MS (ES+) 469.5 (M+H)+ 1H NMR (CDCl3) δ 1.52-1.58 (m, 2H), 1.65-1.72 (m, 2H), 1.87-1.95 (m, 1H), 2.12-2.21 (m, 1H), 2.82-2.90 (m, 1H), 3.02-3.15 (m, 5H), 3.33 (t, 2H), 3.52 (t, 2H), 3.65 (s, 2H), 3.78 (s, 3H), 3.94-3.97 (m, 1H), 6.82-6.87 (m, 2H), 7.12-7.17 (m, 3H), 7.35 (d, 1H), 8.24 (d, 1H), 8.28 (s, 1H), 8.78 (d, 2H). [α]D20=+43.2 deg (c=8 mg/mL, MeOH).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was azeotroped with toluene
  3. custompartitioned between 1N NaOH (50 mL) and ethyl acetate (50 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude product was purified on an Analogix (Analogix Inc., Burlington, Wis.) 24 g silica column (1-15% MeOH in DCM in 30 minutes)
  8. customto give the product as a light foam
  9. filtrationfiltered

Sources & evidence

ORD record
ord-a64649792915478789fca8374099b28d
Source dataset
uspto-grants-2013_12
Patent number
US08609680B2

Reaction notes

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