1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86598174, compound

HRID 458463Notes

Reaction equation

HRID 458463 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:18]([CH2:19][CH2:20][C:21]([F:24])([F:23])[F:22])=[N:17][C:9]2[C@H:10]3[N:14]([C:15](=[O:16])[C:8]=2[C:7]=1[C:25]1[CH:33]=[CH:32][C:28]([C:29]([OH:31])=O)=[CH:27][CH:26]=1)[CH2:13][CH2:12][CH2:11]3)=[O:5])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH2:55][C@H:56]1[C:64]2[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=2)[CH2:58][CH2:57]1>ClCCl>[C@H:56]1([NH:55][C:29]([C:28]2[CH:32]=[CH:33][C:25]([C:7]3[C:8]4[C:15](=[O:16])[N:14]5[C@H:10]([C:9]=4[N:17]=[C:18]([CH2:19][CH2:20][C:21]([F:23])([F:22])[F:24])[C:6]=3[C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:11][CH2:12][CH2:13]5)=[CH:26][CH:27]=2)=[O:31])[C:64]2[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=2)[CH2:58][CH2:57]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2733933(R)-(-)-1-AminoindanHCID 69742483HCID 69742483, compound

Product 1

HCID 86598174HCID 86598174, compoundYield 49.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-[(9aS)-3-(ethoxycarbonyl)-5-oxo-2-(3,3,3-trifluoropropyl)-7,8,9,9a-tetrahydro-5H-pyrido[2,3-α]pyrrolizin-4-yl]benzoic acid (0.075 g, 0.162 mmol) in 1 mL of dichloromethane, EDCI (0.037 g, 0.194 mmol), HOBT (0.026 g, 0.194 mmol) and (R)-(−)-1-aminoindane (0.051 g, 0.324 mmol) were added. The reaction mixture was allowed to stir for ˜3 h. The mixture was then concentrated and redissolved in 1 mL of ethyl acetate. The organics were then washed with saturated aqueous NaHCO3 and brine. Filtration followed by concentration provided a brown oil which was purified by radial chromatography (ethyl acetate/hexanes (4:1)) to yield 0.046 g (49%) of the desired product as a white solid: 1H NMR (CDCl3, 400 MHz) δ 7.86–7.77 (d, 2H, J=8.27), 7.45–7.37 (d, 2H, J=8.28), 7.36–7.29 (d, 1H, J=6.38), 7.28–7.16 (m, 3H), 6.48–6.37 (m, 1H), 5.72–5.64 (q, 1H, J=7.59), 4.71–4.63 (dd, 1H, J=10.34, J=6.21), 4.13–3.96 (m, 2H), 3.72–3.58 (m, 1H), 3.38–3.26 (m, 1H), 3.22–3.08 (m, 2H), 3.07–2.96 (m, 1H), 2.96–2.83 (m, 1H), 2.79–2.56 (m, 3H), 2.55–2.38 (m, 1H), 2.38–2.22 (m, 2H), 1.98–1.84 (m, 1H), 1.45–1.27 (m, 1H), 1.04–0.95 (t, 3H, J=7.07); TLC (EtOAc/Hex(4:1)): Rf=0.3; RP-HPLC (BDS Hypersil C-18 25 cm×4.6 mm; 10–100% CH3CN in H2O with 0.1% TFA buffer, 30 minutes; 1 mL/min) tr=11.8 min, 94.1% purity.

Workup

  1. concentrationThe mixture was then concentrated
  2. dissolutionredissolved in 1 mL of ethyl acetate
  3. washThe organics were then washed with saturated aqueous NaHCO3 and brine
  4. filtrationFiltration
  5. concentrationfollowed by concentration
  6. customprovided a brown oil which
  7. customwas purified by radial chromatography (ethyl acetate/hexanes (4:1))

Sources & evidence

ORD record
ord-8dfaa70ba38541bdb5c3347dcc9ba152
Source dataset
uspto-grants-2007_03
Patent number
US07189851B2

Reaction notes

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