2-Bromoacetamide → HCID 178461910, compound

HRID 243303Notes

Reaction equation

HRID 243303 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.Br[CH2:29][C:30]([NH2:32])=[O:31].CCN(C(C)C)C(C)C>>[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]([CH2:29][C:30]([NH2:32])=[O:31])[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

4

Reactant 3

HCID 696322-BromoacetamideHCID 81531DiisopropylethylamineHCID 178461909HCID 178461909, compound

Product 1

HCID 178461910HCID 178461910, compound

Conditions

Temperature
70 °C

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-bromo-acetamide (57 mg, 0.414 mmol) and DIPEA (215 mL, 1.24 mmol) in IMS (2 mL) was stirred in a sealed vial at 70° C. for 20 h. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM). The product containing fractions were concentrated in vacuo and the resulting residue was triturated with MeOH affording 133 (59 mg, 34%). LCMS: RT 1.80 min [M+H]+ 420.1. 1H NMR (DMSO, 400 MHz): δ 8.25 (1H, s), 8.14 (1H, s), 8.01-7.90 (1H, m), 7.74-7.66 (1H, m), 7.63-7.55 (1H, m), 7.28-7.03 (4H, m), 5.95 (1H, bs), 4.75 (1H, br), 3.04-2.86 (4H, m), 2.74 (1H, bd, J=11.16 Hz), 2.24 (1H, bt, J=11.70 Hz), 1.80-1.55 (5H, m), 1.35-1.19 (1H, m)

Workup

  1. temperatureAfter cooling to RT
  2. customvolatiles were removed under reduced pressure
  3. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM)
  4. additionThe product containing fractions
  5. concentrationwere concentrated in vacuo
  6. customthe resulting residue was triturated with MeOH affording 133 (59 mg, 34%)

Sources & evidence

ORD record
ord-20f6a72351704b899bcd29f8f9ddbc1c
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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