Acetic Acid → Tert-butyl (3-((2-((3-(benzyloxy)-4-(2-methoxyethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate

HRID 2274264Notes

Reaction equation

HRID 2274264 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:13]=[CH:14][C:15]=1[O:16][CH2:17][CH2:18][O:19][CH3:20])[NH2:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:22]1[N:27]=[C:26]([NH:28][C:29]2[CH:30]=[C:31]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH:32]=[CH:33][CH:34]=2)[C:25]([F:43])=[CH:24][N:23]=1.CC(O)=O.CCCCCC.C(OCC)(=O)C>C(O)C.O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([NH:12][C:22]2[N:27]=[C:26]([NH:28][C:29]3[CH:30]=[C:31]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:39])([CH3:40])[CH3:41])[CH:32]=[CH:33][CH:34]=3)[C:25]([F:43])=[CH:24][N:23]=2)[CH:13]=[CH:14][C:15]=1[O:16][CH2:17][CH2:18][O:19][CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 21226206Ethyl acetate hexaneHCID 59174297Tert-butyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)carbamateHCID 867243363-(Benzyloxy)-4-(2-methoxyethoxy)aniline

Product 1

HCID 86724337Tert-butyl (3-((2-((3-(benzyloxy)-4-(2-methoxyethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)carbamateYield 37%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of 3-(benzyloxy)-4-(2-methoxyethoxy)aniline (0.500 g) and tert-butyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate (0.556 g) in ethanol (10 mL), was added CH3COOH (54 mg). The reaction mixture was heated to reflux for 24 hr. Completion of reaction was monitored by TLC using hexane:ethyl acetate (5:5) as mobile phase. After completion, reaction mixture was allowed to cool at room temperature and poured into cold water. Product was extracted with ethyl acetate (50 mL×3). Ethyl acetate layer washed with 50 mL brine solution. Ethyl acetate layer was dried over sodium sulfate and concentrated under reduced pressure. Crude material was purified by using Combiflash chromatography. Desired spot eluted with 18% ethyl acetate in hexane to give 0.35 g of tert-butyl (3-((2-((3-(benzyloxy)-4-(2-methoxyethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate. 1H NMR: DMSO-d6 (400 MHz): 1.467 (s, 9H), 3.357 (s, 3H), 3.614-3.636 (t, 2H, J=4.4), 4.024-4.046 (t, 2H, J=4.0), 4.921 (s, 2H), 6.811-6.833 (d, 1H, J=8.8), 7.120-7.197 (m, 3H), 7.311-7.448 (m, 7H), 7.827 (s, 1H), 8.05-8.068 (d, 1H, J=3.6), 8.935 (s, 1H), 9.306 (s, 1H), 9.353 (s, 1H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 24 hr
  3. customCompletion of reaction
  4. customAfter completion, reaction mixture
  5. extractionProduct was extracted with ethyl acetate (50 mL×3)
  6. washEthyl acetate layer washed with 50 mL brine solution
  7. dry with materialEthyl acetate layer was dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customCrude material was purified
  10. washDesired spot eluted with 18% ethyl acetate in hexane

Sources & evidence

ORD record
ord-d76994645ae14725a5647d59e56498f5
Source dataset
uspto-grants-2015_09
Patent number
US09126950B2

Reaction notes

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