N,N-Dimethylglycine → HCID 178461914, compound

HRID 243304Notes

Reaction equation

HRID 243304 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.[CH3:28][N:29]([CH2:31][C:32](O)=[O:33])[CH3:30].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:32](=[O:33])[CH2:31][N:29]([CH3:30])[CH3:28])[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 673N,N-DimethylglycineHCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178461909HCID 178461909, compound

Product 1

HCID 178461914HCID 178461914, 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), dimethylaminoacetic acid (47 mg, 0.455 mmol), HOAt (62 mg, 0.455 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (87 mL, 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 134 (55 mg, 30%). LCMS: RT 1.79 min [M+H]+ 448.1. 1H NMR (DMSO, 400 MHz): δ 8.23-7.93 (3H, m), 7.90-7.78 (1H, m), 7.68-7.58 (1H, m), 7.21-7.12 (2H, m), 4.80-4.69 (1H, br), 4.53-4.30 (1H, m), 4.22 (0.6H, bd, J=12.25 Hz), 4.03 (0.4H, bd, J=12.25 Hz), 3.85 (0.6H, t, J=12.08 Hz), 3.44-3.26 (1.4H, t, J=12.08 Hz), 3.21-3.10 (1H, m), 2.99 (0.4H, bd, J=13.04 Hz), 2.90-2.64 (1.6H, m), 2.44-2.26 (1H, m), 2.25-2.11 (6H, m), 1.85-1.58 (5H, m), 1.13-0.97 (1H, m). Signals split due to presence of rotamers

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 134 (55 mg, 30%)
  4. customSignals split due to presence of rotamers

Sources & evidence

ORD record
ord-51a5c93e070a4cbe8f266ba80430b05a
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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