4-Methylmorpholine → HCID 58459340, compound

HRID 2036564Notes

Reaction equation

HRID 2036564 reaction equation
[NH:1]([C:7]([O:9][CH2:10][CH:11]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]2[C:12]1=[CH:13][CH:14]=[CH:15][CH:16]=2)=[O:8])[C@H:2]([C:4](O)=[O:5])[CH3:3].CN1CCOCC1.ClC(OCC(C)C)=O.[F:39][C:40]1[CH:45]=[C:44]([NH:46][C:47]2[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=2)[C:43]([NH2:54])=[CH:42][CH:41]=1.[NH4+].[Cl-]>C(Cl)Cl>[F:39][C:40]1[CH:41]=[CH:42][C:43]([NH:54][C:4](=[O:5])[C@@H:2]([NH:1][C:7](=[O:8])[O:9][CH2:10][CH:11]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[C:18]3[C:23]2=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH3:3])=[C:44]([NH:46][C:47]2[CH:48]=[CH:49][C:50]([F:53])=[CH:51][CH:52]=2)[CH:45]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 62365Isobutyl chloroformateHCID 6364642N-((9H-Fluoren-9-ylmethoxy)carbonyl)-L-alanineHCID 13530360HCID 13530360, compound

Product 1

HCID 58459340HCID 58459340, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

To a −10° C. solution (NaCl-ice bath) of Fmoc-L-Ala-OH (4.45 g, 14.30 mmol) and N-methylmorpholine (1.573 mL, 14.30 mmol) in DCM (34.1 mL) was added isobutyl chloroformate (1.782 mL, 13.62 mmol). The resulting cloudy colorless mixture was stirred at −10° C. for 30 min. To the mixture was then added a solution of 5-fluoro-N1-(4-fluorophenyl)benzene-1,2-diamine (1.500 g, 6.81 mmol) in DCM (12.75 mL). The resulting mixture was stirred at −10° C. for 1 h, to which the cold mixture was added satd. aq. NH4Cl solution (100 mL). The precipitate was collected by filtration and washed with water (100 mL) to give (S)-(9H-fluoren-9-yl)methyl 1-(4-fluoro-2-(4-fluorophenylamino)phenylamino)-1-oxopropan-2-ylcarbamate as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 9.42 (1H, s), 7.89 (2H, d, J=7.6 Hz), 7.63-7.78 (3H, m), 7.22-7.46 (6H, m), 6.96-7.14 (4H, m), 6.83 (1H, dd, J=11.2, 2.7 Hz), 6.67 (1H, td, J=8.5, 2.8 Hz), 4.11-4.33 (4H, m), 1.28 (3H, d, J=7.0 Hz); LC-MS (ESI) m/z 514.2 [M+H]+. The off-white solid was carried on crude without purification.

Workup

  1. stirringThe resulting mixture was stirred at −10° C. for 1 h, to which the cold mixture
  2. additionwas added satd
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with water (100 mL)

Sources & evidence

ORD record
ord-e9c9b56e4d7d4bf8a2a0bd8620737d68
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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