4-Methylmorpholine → {(S)-1-[4-fluoro-2-(pyridin-2-ylamino)phenylcarbamoyl]ethyl}carbamic acid tert-butyl ester

HRID 242943Notes

Reaction equation

HRID 242943 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[C:5]([NH2:8])=[CH:6][CH:7]=1.[C:16]([O:20][C:21]([NH:23][C@@H:24]([CH3:28])[C:25](O)=[O:26])=[O:22])([CH3:19])([CH3:18])[CH3:17].C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.C([O-])(O)=O.[Na+]>[C:16]([O:20][C:21](=[O:22])[NH:23][C@H:24]([C:25](=[O:26])[NH:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=1[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1)[CH3:28])([CH3:17])([CH3:18])[CH3:19]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 681571794-Fluoro-N2-pyridin-2-ylbenzene-1,2-diamine

Product 1

HCID 68158207{(S)-1-[4-fluoro-2-(pyridin-2-ylamino)phenylcarbamoyl]ethyl}carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 4-fluoro-N2-pyridin-2-ylbenzene-1,2-diamine (241 mg, 1.19 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (247 mg, 1.30 mmol), HOAt (178 mg, 1.30 mmol), 4-methylmorpholine (0.287 mL, 2.61 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (250 mg, 1.30 mmol) in DCM (10 mL) was stirred at RT for 2 h. The reaction mixture was diluted with a saturated aqueous solution of NaHCO3 and extracted with DCM (×3). The combined organic fractions were passed through a phase separator and concentrated in vacuo to afford {(S)-1-[4-fluoro-2-(pyridin-2-ylamino)phenylcarbamoyl]ethyl}carbamic acid tert-butyl ester as a pale red solid (505 mg, quantitative). LCMS (Method B): RT 2.30 min [M+H]+ 375.0.

Workup

  1. extractionextracted with DCM (×3)
  2. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2458ed2a39e049e9ad2a33418e2c38aa
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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