Cyclopropylamine → HCID 54675653, compound

HRID 2203375Notes

Reaction equation

HRID 2203375 reaction equation
[NH2:1][C:2]1[C:3]2[C:25]([CH3:31])([C:26](OCC)=[O:27])[C:24](=[O:32])[NH:23][C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][CH2:18][C:19]([F:22])([F:21])[F:20])[N:9]=2)[N:7]=1.[CH:33]1([NH2:36])[CH2:35][CH2:34]1>>[NH2:1][C:2]1[C:3]2[C:25]([CH3:31])([C:26]([NH:36][CH:33]3[CH2:35][CH2:34]3)=[O:27])[C:24](=[O:32])[NH:23][C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][CH2:18][C:19]([F:20])([F:22])[F:21])[N:9]=2)[N:7]=1

Participants

3

Reactant 2

HCID 69828CyclopropylamineHCID 86679012HCID 86679012, compound

Product 1

HCID 54675653HCID 54675653, compound

Procedure

To the intermediate from Step A above (165 mg, 0.367 mmol) was added cyclopropylamine (3.31 mL, 47.7 mmol) and the resultant mixture heated to 50° C. for 16 hours. The reaction mixture was concentrated in vacuo and the residue purified by silica gel column chromatography using a DCM/MeOH (with 0.5% NH4OH) gradient. Chiral separation using SFC on a Chiralcel OJ-H column provided both enantiomers of the title compound. 1H NMR (500 MHz, DMSO-d6): δ 11.23 (1H, s), 9.02 (1H, dd, J=8.08, 1.55 Hz), 8.62 (1H, dd, J=4.50, 1.57 Hz), 7.64 (1H, d, J=4.05 Hz), 7.37 (1H, dd, J=8.08, 4.49 Hz), 6.76 (2H, s), 4.81 (2H, t, J=6.60 Hz), 3.06-2.94 (2H, m), 2.67-2.60 (1H, m), 1.55 (3H, s), 0.62-0.53 (2H, m), 0.50-0.41 (2H, m). m/z=461.3 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue purified by silica gel column chromatography
  3. customChiral separation

Sources & evidence

ORD record
ord-064750f7797a4903a5c09a6975f622e4
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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