4-Chloro-5-iodopyrimidine → 3'-[(5-Iodopyrimidin-4-yl)amino]-6-methylbiphenyl-3-carboxylic acid

HRID 77719Notes

Reaction equation

HRID 77719 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]([C:15]([OH:17])=[O:16])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl[C:19]1[C:24]([I:25])=[CH:23][N:22]=[CH:21][N:20]=1>C(O)(C)C>[I:25][C:24]1[C:19]([NH:1][C:2]2[CH:3]=[C:4]([C:8]3[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]([C:15]([OH:17])=[O:16])[CH:9]=3)[CH:5]=[CH:6][CH:7]=2)=[N:20][CH:21]=[N:22][CH:23]=1

Participants

4

Reactant 2

HCID 112302044-Chloro-5-iodopyrimidineHCID 690425833'-Amino-6-methyl-[1,1'-biphenyl]-3-carboxylic acid

Product 1

HCID 690440573'-[(5-Iodopyrimidin-4-yl)amino]-6-methylbiphenyl-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

3′-Amino-6-methylbiphenyl-3-carboxylic acid (3.00 g, 0.0132 mol) was mixed with 4-chloro-5-iodopyrimidine (3.30 g, 0.0137 mol) and isopropyl alcohol (60 mL). The resulting mixture was heated to 80° C., at which temperature solution occurred. A short time later, the product began to precipitate. After 2 h, HPLC showed 95% conversion of to product. HPLC Method: Zorbax SB C18, 5 μm, 15 cm, 35 C, flow 1.2 mL/min, 25% CH3CN—H20 (0.05% TFA), to 100% CH3CN in 8.0 min; stop time 11 min; detector 254 &220 nm; retention time starting material, 2.8 min (UVmax 205 & 230 nm); pyrimidine, 4.8 min (UVmax 240 & 270 nm); product, 4.9 min (UV max 204, 228, & 290 nm). The reaction was cooled to 20° C. The product was isolated by filtration, rinsed with iPrOH, then vacuum dried. Yield 5.35 g of a light tan powder. The product is believed to be the HCl salt or partial salt. 1H NMR (300 MHz, DMSO) δ 9.62 (br s, 1H, NH); 8.83 (s, 1H); 8.69 (s, 1H); 7.83 (dd, 1H); 7.76 (d, 1H); 7.42-7.58 (m, 4H); 7.25 (dt, 1H); 2.33 (s, 3H).

Workup

  1. customto precipitate
  2. waitto 100% CH3CN in 8.0 min
  3. customtime 11 min
  4. custommaterial, 2.8 min (UVmax 205 & 230 nm)
  5. custompyrimidine, 4.8 min (UVmax 240 & 270 nm)
  6. customproduct, 4.9 min (UV max 204, 228, & 290 nm)
  7. temperatureThe reaction was cooled to 20° C
  8. customThe product was isolated by filtration
  9. washrinsed with iPrOH
  10. customvacuum dried

Sources & evidence

ORD record
ord-5474e7dab8d34d38a8785da54da66e40
Source dataset
uspto-grants-2014_09
Patent number
US08841318B2

Reaction notes

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