Lithium Hydroxide → HCID 68863976, compound

HRID 1725992Notes

Reaction equation

HRID 1725992 reaction equation
C[O:2][C:3]([C:5]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[CH:8]=[C:7](/[CH:15]=[CH:16]/[C:17](O)=[O:18])[C:6]=1[NH:20][S:21]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)(=[O:23])=[O:22])=[O:4].C1CCC(N=C=NC2CCCCC2)CC1.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[NH2:65][CH2:66][CH2:67][CH:68]1[CH2:72][CH2:71][CH2:70][N:69]1[CH3:73].[Li+].[OH-]>CN(C=O)C>[CH3:73][N:69]1[CH2:70][CH2:71][CH2:72][CH:68]1[CH2:67][CH2:66][NH:65][C:17](=[O:18])/[CH:16]=[CH:15]/[C:7]1[C:6]([NH:20][S:21]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)(=[O:23])=[O:22])=[C:5]([C:3]([OH:2])=[O:4])[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[CH:8]=1

Participants

8

Reactant 6

HCID 3939Lithium HydroxideHCID 10868DicyclohexylcarbodiimideHCID 81531DiisopropylethylamineHCID 983882-(2-Aminoethyl)-1-methylpyrrolidineHCID 27960291-Hydroxybenzotriazole hydrateHCID 68866001HCID 68866001, compound

Product 1

HCID 68863976HCID 68863976, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of Example 476D (20 mg, 0.05 mmol) in DMF (1.0 mL) was treated with macroporous polystyrene bound DCC resin (105 mg, 0.14 mmol), 1-hydroxybenzotriazole hydrate (7 mg, 0.05 mmol), diisopropylethylamine (0.026 mL, 0.15 mmol) and 2-(aminoethyl)-1-methylpyrrolidine (0.010 mL, 0.07 mmol), heated to 55° C. for 16 hours, and concentrated. The concentrate was dissolved in 0.5 mL 2:1 dioxane/water, treated with LiOH (13 mg, 0.3 mmol), and heated to 160° C. for 27.5 minutes in a microwave reactor. The reaction mixture was concentrated and the residue was purified by C18 reverse-phase HPLC using acetonitrile/water/0.1% TFA to provide the desired product. MS (DCI) m/e 512 (M+H)+; 1H NMR (500 MHz, DMSO-d6) δ 12.89 (br s, 1H), 9.37 (br s, 1H), 7.99 (t, 1H), 7.61 (d, 2H), 7.54 (t, 1H), 7.46-7.43 (m, 3H), 7.31 (s, 1H), 6.28 (d, 1H), 3.23 (m, 4H), 3.08 (m, 1H), 2.84 (d, 3H), 2.75 (m, 2H), 2.65 (m, 2H), 2.30 (m, 1H), 2.04 (m, 2H), 1.90 (m, 1H), 1.71-1.63 (m, 6H).

Workup

  1. concentrationconcentrated
  2. dissolutionThe concentrate was dissolved in 0.5 mL 2:1 dioxane/water
  3. temperatureheated to 160° C. for 27.5 minutes in a microwave reactor
  4. concentrationThe reaction mixture was concentrated
  5. customthe residue was purified by C18 reverse-phase

Sources & evidence

ORD record
ord-d6e631fd70d043948300b6f1f886e946
Source dataset
uspto-grants-2009_02
Patent number
US07491718B2

Reaction notes

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