4-Methylmorpholine → HCID 178461913, compound

HRID 243305Notes

Reaction equation

HRID 243305 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:16]([NH:18][C:19]2[N:27]=[CH:26][N:25]=[C:24]3[C:20]=2[N:21]=[CH:22][NH:23]3)[CH3:17])[CH2:2]1.[OH:28][C:29]([CH3:34])([CH3:33])[C:30](O)=[O:31].C1C=NC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.CN1CCOCC1>C(Cl)Cl>[N:27]1[C:19]([NH:18][C@H:16]([C:8]2[N:7]([C@@H:3]3[CH2:4][CH2:5][CH2:6][N:1]([C:30](=[O:31])[C:29]([OH:28])([CH3:34])[CH3:33])[CH2:2]3)[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=2)[CH3:17])=[C:20]2[C:24]([NH:23][CH:22]=[N:21]2)=[N:25][CH:26]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 116712-Hydroxyisobutyric acidHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178461909HCID 178461909, compound

Product 1

HCID 178461913HCID 178461913, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of [(S)-1-((R)-1-piperidin-3-yl-1H-benzoimidazol-2-yl)ethyl]-(9H-purin-6-yl)amine from Example 16 (150 mg, 0.414 mmol), 2-hydroxy-2-methylpropionic acid (47 mg, 0.455 mmol), HOAt (62 mg, 0.455 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (87 μL, 0.455 mmol) and 4-methylmorpholine (0.10 mL, 0.911 mmol) in anhydrous DCM (4 mL) was stirred at RT for 20 h. Volatiles were removed in vacuo and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM) then triturated with diethyl ether affording 135 (65 mg, 35%). LCMS: RT 2.44 min [M+H]+ 449.1. 1H NMR (DMSO, 400 MHz): δ 8.24-7.90 (3H, m), 7.88-7.81 (1H, m), 7.67-7.56 (1H, m), 7.23-7.07 (2H, m), 5.90 (1H, s), 5.51 (1H, s), 5.30-3.76 (4H, br), 2.45-2.28 (1H, m), 1.93-1.61 (5H, m), 1.48-1.27 (6H, m), 1.20-1.08 (1H, m)

Workup

  1. customVolatiles were removed in vacuo
  2. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM)
  3. customthen triturated with diethyl ether affording 135 (65 mg, 35%)

Sources & evidence

ORD record
ord-2c42a32ecd7440a49c929b377b603349
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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