2-(Dimethylamino)ethanol → HCID 58415448, compound

HRID 46182Notes

Reaction equation

HRID 46182 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:21][CH2:22][C:23]([N:25]3[CH:29]([CH3:30])[CH2:28][CH2:27][CH:26]3[CH3:31])=[O:24])[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([OH:17])[CH:15]=3)[C:10]3=[N:18][CH:19]=[CH:20][N:9]23)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:51][N:52]([CH3:56])[CH2:53][CH2:54]O.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:21][CH2:22][C:23]([N:25]3[CH:26]([CH3:31])[CH2:27][CH2:28][CH:29]3[CH3:30])=[O:24])[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH2:54][CH2:53][N:52]([CH3:56])[CH3:51])[CH:15]=3)[C:10]3=[N:18][CH:19]=[CH:20][N:9]23)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 79022-(Dimethylamino)ethanol2×HCID 11776Triphenylphosphine2×HCID 5363146Diisopropyl azodicarboxylate2×HCID 1361955845-(4-chlorophenyl)-5-[3-(2,5-dimethylpyrrolidin-1-yl)-3-oxopropyl]-5H-imidazo[2,1-a]isoindol-7-ol

Product 1

HCID 58415448HCID 58415448, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(4-chlorophenyl)-5-[3-(2,5-dimethylpyrrolidin-1-yl)-3-oxopropyl]-5H-imidazo[2,1-a]isoindol-7-ol (30 mg) in dry THF (0.5 mL) was added triphenylphosphine (27 mg), 2-dimethylaminoethanol (11 μL), then DIAD (21 μL) at room temperature. After 3 h additional triphenylphosphine (27 mg), 2-dimethylaminoethanol (11 μL), and DIAD (21 μL) were added and stirring continued. After 24 h the mixture was concentrated. The crude material was purified by preparative reversed-phase HPLC (20×150 mm Waters Sunfire, 5-50% ACN/water containing 0.1% TFA over 20 min. at 20 mL/min). Fractions containing the product were pooled then passed through Dowex 1×2-400 ion exchange resin (prewashed with 1M NaOH, H2O, MeOH) washing with MeOH. The filtrate was concentrated to give a white solid (20 mg): 1H-NMR (500 MHz, CDCl3) δ 7.73 (dd, J=2.2 and 6.1 Hz, 1 H), 7.29-7.24 (m, 3 H), 7.12 (m, 2 H), 6.93 (m, 2 H), 6.78 (dd, J=2.2 and 3.9 Hz, 1 H), 4.04-3.90 (m, 3 H), 3.40 (m, 1 H), 3.11-2.79 (m, 2 H), 2.69 (t, J=5.37 Hz, 1 H), 2.32 (s, 6 H), 2.02-1.75 (m, 2 H), 1.66-1.49 (m, 5 H), 1.16 (dd, J=6.35 and 11.96 Hz, 3 H), 0.88 (dd, J=6.32 and 27.1 Hz, 3 H); HRMS (M+H)+ calculated 507.2521. found 507.2508.

Workup

  1. customat room temperature
  2. concentrationAfter 24 h the mixture was concentrated
  3. customThe crude material was purified by preparative reversed-phase HPLC (20×150 mm Waters Sunfire, 5-50% ACN/water containing 0.1% TFA over 20 min. at 20 mL/min)
  4. additionFractions containing the product
  5. washwashing with MeOH
  6. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-0187920a57674993bed50a25442e5d8a
Source dataset
uspto-grants-2013_09
Patent number
US08541595B2

Reaction notes

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