Aniline → N4-(6-aminopyridin-2-yl)-N6-phenylpyrimidine-4,6-diamine

HRID 2193634Notes

Reaction equation

HRID 2193634 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5](OC)=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19](F)=[C:18](Cl)[CH:17]=3)[N:12]=[CH:11][N:10]=2)C=1.[NH2:26]C1C=CC=CC=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[NH2:26][C:2]1[N:1]=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6115AnilineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58434677N-(5-amino-2-methoxyphenyl)-N'-(3-chloro-4-fluorophenyl)pyrimidine-4,6-diamine2×

Product 1

HCID 57708273N4-(6-aminopyridin-2-yl)-N6-phenylpyrimidine-4,6-diamineYield 47.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

The preparation of N4-(5-amino-2-methoxyphenyl)-N6-(3-chloro-4-fluorophenyl)pyrimidine-4,6-diamine (1) is described in Example 7 (Int-G). To a stirred solution of 1 (150 mg, 0.41 mmol) in DMF (8 mL) was added 2 (137 mg, 0.83 mmol), HATU (317 mg, 0.83 mmol) and DIPEA (215 mg, 1.67 mmol) at 0° C. The reaction mixture was stirred for 18 h at RT. After the completion of reaction (monitored by TLC), the crude mixture was diluted with water and extracted with EtOAc (4×100 mL). The organic layers were dried over anhydrous Na2SO4 and concentrated under vacuo to afford 3 (100 mg, 47.3%) as off-white solid, which was used in the next step without further purification. 1H NMR (CDCl3, 500 MHz): δ 8.35 (s, 1H), 8.12 (s, 1H), 7.48-7.43 (m, 1H), 7.24 (s, 1H), 7.16-7.10 (m, 2H), 7.03 (s, 1H), 6.84 (t, J=9.0 Hz, 2H), 6.49 (s, 1H), 6.15 (s, 1H), 5.29 (s, 1H), 3.85 (s, 3H), 3.33 (d, J=5.0 Hz, 2H), 2.80 (s, 3H). Mass: m/z 506 (M++1).

Workup

  1. customAfter the completion of reaction (monitored by TLC)
  2. extractionextracted with EtOAc (4×100 mL)
  3. dry with materialThe organic layers were dried over anhydrous Na2SO4
  4. concentrationconcentrated under vacuo

Sources & evidence

ORD record
ord-2f62243ce32d4a4bada0a8675a6e161a
Source dataset
uspto-grants-2012_12
Patent number
US08329901B2

Reaction notes

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