Triethylamine → 5-(4-(2-aminopyridin-4-yloxy)-3-fluorophenyl)-3-benzyl-2-(4-fluorophenylamino)pyrimidin-4(3H)-one

HRID 2246477Notes

Reaction equation

HRID 2246477 reaction equation
[CH2:1]([N:8]1[C:13](=[O:14])[C:12]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([F:22])[CH:16]=2)=[CH:11][N:10]=[C:9]1[NH:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:32]1[CH:37]=[CH:36][N:35]=[C:34]([NH2:38])[CH:33]=1.CCN(CC)CC>CN1C(=O)CCC1.CN(C1C=CN=CC=1)C.C(Cl)Cl>[NH2:38][C:34]1[CH:33]=[C:32]([O:21][C:18]2[CH:19]=[CH:20][C:15]([C:12]3[C:13](=[O:14])[N:8]([CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[C:9]([NH:23][C:24]4[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=4)=[N:10][CH:11]=3)=[CH:16][C:17]=2[F:22])[CH:37]=[CH:36][N:35]=1

Participants

7

Reactant 3

HCID 8471Triethylamine2×HCID 5818662-Amino-4-chloropyridine2×HCID 592183623-benzyl-5-(3-fluoro-4-hydroxyphenyl)-2-(4-fluorophenylamino)pyrimidin-4(3H)-one

Product 1

HCID 592183715-(4-(2-aminopyridin-4-yloxy)-3-fluorophenyl)-3-benzyl-2-(4-fluorophenylamino)pyrimidin-4(3H)-one

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

3-benzyl-5-(3-fluoro-4-hydroxyphenyl)-2-(4-fluorophenylamino)pyrimidin-4(3H)-one (731.4 mg, 1.804 mmol) and 4-chloropyridin-2-amine (473.7 mg, 3.685 mmol) were dissolved in NMP (8.0 ml) and Et3N (1.25 ml, 8.97 mmol) was added. The flask was fitted with a reflux condenser and placed in a preheated oil bath (190 C) and stirred under nitrogen. After 19 hours, more 4-chloropyridin-2-amine (409 mg, 3.20 mmol), DMAP (286.5 mg, 2.345 mmol), Et3N (0.50 ml, 3.6 mmol) were added, followed by NMP (1.0 ml). Stirring was continued at 190 C. After 23 hours, the reaction was cooled to room temperature, diluted with DCM, and washed with water (2×50 ml). The aqueous extracts were combined and extracted with DCM. Some MeOH (˜10%) was also used to help solubilize the biphasic mixture. All the organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on silica gel (˜3 inches, DCM->50:1->20:1 DCM/MeOH) to afford the desired 5-(4-(2-aminopyridin-4-yloxy)-3-fluorophenyl)-3-benzyl-2-(4-fluorophenylamino)pyrimidin-4(3H)-one, which was taken on to the next step. MS (ESI pos. ion) m/z: 498 (MH+). Calc'd exact mass for C28H21F2N5O2: 497.

Workup

  1. customThe flask was fitted with a reflux condenser
  2. customplaced in a preheated oil bath
  3. stirringStirring
  4. waitAfter 23 hours
  5. washwashed with water (2×50 ml)
  6. extractionextracted with DCM
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified on silica gel (˜3 inches, DCM->50:1->20:1 DCM/MeOH)

Sources & evidence

ORD record
ord-54a829225d204537a7fc3cf2af07f9f6
Source dataset
uspto-grants-2010_03
Patent number
US07687522B2

Reaction notes

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