Lithium Hydroxide → HCID 68492872, compound

HRID 1822478Notes

Reaction equation

HRID 1822478 reaction equation
C([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([NH2:19])[CH2:16][N:15]2[C:20](=[O:40])[NH:21][CH:22]([C:27](=[O:39])[NH:28][CH:29]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:31][CH:30]2[OH:38])[C:23]([CH3:26])([CH3:25])[CH3:24])=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])C.CCN(C(C)C)C(C)C.Cl.[C:51](Cl)(=[O:58])[C:52]1[CH:57]=[CH:56][CH:55]=[N:54][CH:53]=1.C(O)C(N)(CO)CO.[Li+].[OH-]>C(Cl)Cl.C(O)(=O)C>[OH:38][CH:30]1[CH2:31][C:32]2[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:29]1[NH:28][C:27]([CH:22]([NH:21][C:20]([N:15]1[CH2:16][CH:17]([NH:19][C:51]([C:52]2[CH:53]=[N:54][CH:55]=[CH:56][CH:57]=2)=[O:58])[CH2:18][CH:14]1[C:12]([NH:11][C:6]1([C:4]([OH:3])=[O:5])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:13])=[O:40])[C:23]([CH3:26])([CH3:24])[CH3:25])=[O:39]

Participants

8

Reactant 5

HCID 3939Lithium HydroxideHCID 6503Tris(hydroxymethyl)aminomethaneHCID 81531DiisopropylethylamineHCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)HCID 68495228HCID 68495228, compound

Product 1

HCID 68492872HCID 68492872, compoundYield 46.9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of compound 151 (35 mg, 0.064 mmol) in DCM (1 ml), was added DIEA (0.12 mmol, 19 μl) and nicotinoyl chloride hydrochloride (0.12 mmol, 17 mg).The solution was stirred at RT for 18 h, PS-trisamine was added then stirred at RT for 4 h. After filtration, the solution was washed with citric acid (10% aq) and NaHCO3 (sat, aq), the organic phase was dried over Na2SO4 and concentrated. The residue was dissolved in THF:MeOH (2:1, 1.5 ml). LiOH (1N aq, 3.2 mmol, 320 μl) was added. The solution was stirred at 60° C. for 24 h. Acetic acid was added and then concentrated. The residue was dissolved in MeOH and subjected to purification by HPLC, affording the title compound (19.5 mg, 0.03 mmol). Purity by HPLC>98%, M+H+633.1.

Workup

  1. stirringthen stirred at RT for 4 h
  2. filtrationAfter filtration
  3. washthe solution was washed with citric acid (10% aq) and NaHCO3 (sat, aq)
  4. dry with materialthe organic phase was dried over Na2SO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in THF:MeOH (2:1, 1.5 ml)
  7. stirringThe solution was stirred at 60° C. for 24 h
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in MeOH
  10. customsubjected to purification by HPLC

Sources & evidence

ORD record
ord-2cd44dd0f78242028e0c85841cb17849
Source dataset
uspto-grants-2009_10
Patent number
US07608590B2

Reaction notes

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