Cyclopropylamine → HCID 58236588, compound

HRID 409972Notes

Reaction equation

HRID 409972 reaction equation
[C:1]([O:5][C:6](=[O:37])[N:7]([CH2:12][C:13]1[CH:14]=[N:15][C:16]([C:19]2[S:27][C:26]3[C:21](=[N:22][CH:23]=[CH:24][C:25]=3[O:28][C:29]3[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][C:30]=3[F:36])[CH:20]=2)=[CH:17][CH:18]=1)[CH2:8][CH2:9][O:10][CH3:11])([CH3:4])([CH3:3])[CH3:2].ClC(Cl)(O[C:42](=[O:48])OC(Cl)(Cl)Cl)Cl.CC[N:52]([CH:56]([CH3:58])[CH3:57])C(C)C.C1(N)CC1>O1CCCC1>[C:1]([O:5][C:6](=[O:37])[N:7]([CH2:12][C:13]1[CH:14]=[N:15][C:16]([C:19]2[S:27][C:26]3[C:21](=[N:22][CH:23]=[CH:24][C:25]=3[O:28][C:29]3[CH:34]=[CH:33][C:32]([NH:35][C:42]([NH:52][CH:56]4[CH2:58][CH2:57]4)=[O:48])=[CH:31][C:30]=3[F:36])[CH:20]=2)=[CH:17][CH:18]=1)[CH2:8][CH2:9][O:10][CH3:11])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 579194724-[[2-[5-[[Boc(2-methoxyethyl)amino]methyl]-2-pyridyl]-7-thieno[3,2-b]pyridyl]oxy]-3-fluoroaniline

Product 1

HCID 58236588HCID 58236588, compoundYield 173.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To amine 126 (0.24 g, 0.46 mmol) in tetrahydrofuran (60 mL) at 0° C. was added triphosgene (0.054 g, 0.18 mmol) and the resulting solution was stirred for 1 h at 0° C. DIPEA (0.40 mL, 0.30 g, 2.3 mmol) and cyclopropylamine (0.26 g, 4.6 mmol) were sequentially added and the mixture was warmed to room temperature and stirred for 3 h, then concentrated under reduced pressure. The residue was partitioned between dichloromethane and water, the organic phase was collected, washed with sat. NH4Cl(aq) and brine, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (ethyl acetate to 5% methanol/ethyl acetate), yielding 338 (0.19 g, 67% yield). MS (m/z): 608.4 (M+H).

Workup

  1. temperaturethe mixture was warmed to room temperature
  2. stirringstirred for 3 h
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was partitioned between dichloromethane and water
  5. customthe organic phase was collected
  6. washwashed with sat. NH4Cl(aq) and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography on silica gel (ethyl acetate to 5% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-3610f712149b4b30856dbdf84e869046
Source dataset
uspto-grants-2014_06
Patent number
US08759522B2

Reaction notes

Loading…