Allylamine → HCID 21090317, compound

HRID 350944Notes

Reaction equation

HRID 350944 reaction equation
[CH2:1]([NH:4][C:5]1[N:6]([C:23]2[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=2[CH3:32])[C:26]([OH:28])=O)[C:7](=[O:22])[C:8]([Cl:21])=[C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[F:20])[N:10]=1)[CH:2]=[CH2:3].ClC(OCC(C)C)=O.CN1CCOCC1.[CH2:48]([NH2:51])[CH:49]=[CH2:50]>CN(C)C(=O)C>[CH2:48]([NH:51][C:26](=[O:28])[C:25]1[CH:29]=[CH:30][C:31]([CH3:32])=[C:23]([N:6]2[C:7](=[O:22])[C:8]([Cl:21])=[C:9]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=3[F:20])[N:10]=[C:5]2[NH:4][CH2:1][CH:2]=[CH2:3])[CH:24]=1)[CH:49]=[CH2:50]

Participants

6

Reactant 4

HCID 7853AllylamineHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 21089150HCID 21089150, compound

Product 1

HCID 21090317HCID 21090317, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) solution of 3-[2-(allylamino)-5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoic acid (from Step 3) (0.37 g, 0.80 mmol) in N,N-dimethylacetamide (2 mL) was added isobutyl chloroformate (0.12 mL, 0.96 mmol) and 4-methylmorpholine (0.11 mL, 1.04 mmol). Stirred at 0° C. for 5 min, ambient temperature for 30 min. Added allyl amine (0.09 mL, 1.20 mmol). Stirred at ambient temperature for 2 h. Purified by preparatory HPLC using a 10–90% CH3CN/H2O (30 min) gradient containing 0.5% TFA at a flow rate of 80 mL/min. Appropriate fractions (M+H m/z=494) were combined, freeze-dried, and lyophilized. Washed with 5% NaHCO3 (20 mL) and extracted with DCM (3×15 mL). The organic extracts were dried over Na2SO4, filtered, concentrated under reduced pressure, and dried in vacuo to give the desired product as a white solid (0.24 g, 60%). 1H NMR (CD3OD/400 MHz) δ7.93 (m, 1H), 7.67 (s, 1H), 7.55 (q, 2H, J=8.0 Hz), 7.00 (t, 2H, J=8.8 Hz), 5.90 (m, 1H), 5.80 (m, 1H), 5.51 (m, 2H), 5.21 (m, 1H), 5.09 (m, 3H), 3.95 (m, 4H), 2.14 (s, 3H). ESHRMS m/z 501.1520 (M+H calculated for C25H24ClF2N4O3 requires 501.1500).

Workup

  1. stirringStirred at ambient temperature for 2 h
  2. customPurified by preparatory HPLC
  3. customa 10–90% CH3CN/H2O (30 min) gradient
  4. additioncontaining 0.5% TFA at a flow rate of 80 mL/min
  5. customfreeze-dried
  6. washWashed with 5% NaHCO3 (20 mL)
  7. extractionextracted with DCM (3×15 mL)
  8. dry with materialThe organic extracts were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customdried in vacuo

Sources & evidence

ORD record
ord-c97334a11d75407b8b450d4ca6b59e9e
Source dataset
uspto-grants-2007_02
Patent number
US07183287B2

Reaction notes

Loading…