Cyclopropylamine → HCID 44229704, compound

HRID 1026833Notes

Reaction equation

HRID 1026833 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([CH2:25][N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[CH:21][N:20]=3)[S:18][C:11]=12)[NH2:5].CC[N:34]([CH:38]([CH3:40])[CH3:39])[CH:35](C)C.ClC(Cl)([O:44]C(=O)OC(Cl)(Cl)Cl)Cl.C1(N)CC1>C1COCC1>[CH:38]1([NH:34][C:35]([NH:5][C:4]2[CH:6]=[CH:7][C:8]([O:9][C:10]3[CH:15]=[CH:14][N:13]=[C:12]4[CH:16]=[C:17]([C:19]5[CH:24]=[CH:23][C:22]([CH2:25][N:26]6[CH2:27][CH2:28][O:29][CH2:30][CH2:31]6)=[CH:21][N:20]=5)[S:18][C:11]=34)=[C:2]([F:1])[CH:3]=2)=[O:44])[CH2:39][CH2:40]1

Participants

6

Reactant 4

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 58207676HCID 58207676, compound

Product 1

HCID 44229704HCID 44229704, compoundYield 37.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The solution of aniline 359 (136 mg, 0.312 mmol) and DIPEA (0.218 mL, 1.246 mmol) in THF (6 mL) was cooled to 0° C., and then triphosgene (46.2 mg, 0.156 mmol) was added and the reaction mixture was stirred for 1 h at 0° C. followed by an addition of cyclopropylamine (89 mg, 1.558 mmol). The reaction mixture was stirred at r.t. for an additional 3 hrs then concentrated, partitioned between water and ethyl acetate. A thick solid was formed which was isolated by suction filtration, rinsed with water and ethyl acetate, and dried in vacuo. This material was then purified using Gilson (eluent 20-95% MeOH/H2O, 1 h) to give the title compound 360 (30 mg, 0.058 mmol, 18.53% yield) as a white solid. 1 HNMR (DMSO-d6) d (ppm) 1H:HNMR 9.16 (s, br, 1H), 8.16 (d, 1H, J=1.6 HZ), 8.11 (d, 1H, J=5.4 Hz), 7.91 (s, 1H), 7.83 (d, 1H, J=8.2 Hz), 7.46 (dd, 1H, J1=2.1 Hz, J2=8.2 Hz), 7.34 (dd, 1H, J1=2.6 Hz, J2=13.9 Hz), 6.97-7.45 (m, 2H), 6.84-6.81 (m, 1H), 6.23 (d, 1H, J=4.7 Hz), 3.18 (t, 4H), 3.14 (s, 2H), 2.15-2.12 (m, 1H), 1.98 (m, 4H), 0.23-0.19 (m, 2H), 0.02-0.005 (m, 2H). MS: 520.4 (MH)+.

Workup

  1. stirringThe reaction mixture was stirred at r.t. for an additional 3 hrs
  2. concentrationthen concentrated
  3. custompartitioned between water and ethyl acetate
  4. customA thick solid was formed which
  5. customwas isolated by suction filtration
  6. washrinsed with water and ethyl acetate
  7. customdried in vacuo
  8. customThis material was then purified
  9. customGilson (eluent 20-95% MeOH/H2O, 1 h)

Sources & evidence

ORD record
ord-b670bc0558d642a3a389adecf23d46ab
Source dataset
uspto-grants-2014_05
Patent number
US08729268B2

Reaction notes

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