Tetrahydrofuran → HCID 71092839, compound

HRID 1522105Notes

Reaction equation

HRID 1522105 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16](N(OC)C)=[O:17])=[CH:11][CH:10]=2)[C:3]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:24][CH:23]=1.[CH2:35]1[CH2:39]OC[CH2:36]1.C([Mg]Br)#CC>>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16](=[O:17])[C:36]#[C:35][CH3:39])=[CH:11][CH:10]=2)[C:3]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)=[CH:24][CH:23]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 71474498HCID 71474498, compoundHCID 178419101HCID 178419101, compound

Product 1

HCID 71092839HCID 71092839, compoundYield 25.9%

Conditions

Temperature
0 °C

Procedure

In a round bottom flask with stirbar was added 2-{4-[6-amino-5-(4-phenoxy-phenyl)-pyrimidin-4-ylamino]-phenyl}-N-methoxy-N-methyl-acetamide (275.0 mg; 0.604 mmol; 1.0 eq.), suspended in THF (2.5 ml; 30.857 mmol; 51.1 eq.). The suspension was cooled to 0° C. At this temperature was added 1-propynylmagnesium bromide (12.1 ml; 6.037 mmol; 10.0 eq.) drop by drop at constant temperature to afford a red solution. After complete addition, the reaction mixture was stirred 30 min at room temperature. The reaction suspension was quenched with aqueous solution of ammonium chloride, and extracted with EtOAc (3×). The combined organic phase were dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was dissolved in DMSO and purified by preparative HPLC to afford 1-(4-(6-amino-5-(4-phenoxyphenyl)-pyrimidin-4-ylamino)-phenyl)-pent-3-yn-2-one (68 mg, 17% yield) as light yellow solid. MS: m/z=435 [M+H]+. 1H-NMR (DMSO-d6) □δ 8.43 (bs, 1H), 8.28 (s, 1H), 7.46 (t, 2H), 7.42 (d, 2h), 7.37 (d, 2H), 7.31-7.13 (m, 7H), 6.99 (bs, 2H), 3.87 (s, 2H), 2.04 (s, 3H).

Workup

  1. customto afford a red solution
  2. additionAfter complete addition
  3. customThe reaction suspension was quenched with aqueous solution of ammonium chloride
  4. extractionextracted with EtOAc (3×)
  5. dry with materialThe combined organic phase were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe crude compound was dissolved in DMSO
  9. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-6260eb98c76f41daacb5bda514d3e382
Source dataset
uspto-grants-2015_07
Patent number
US09073947B2

Reaction notes

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