Tetrahydrofuran → 4-(2'-(2-Hydroxy-2-methylpropylamino)-4'-isopropyl-4,5'-bipyrimidin-2-ylamino)benzonitrile

HRID 2359778Notes

Reaction equation

HRID 2359778 reaction equation
[CH:1]([C:4]1[C:9]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:17]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=3)[N:11]=2)=[CH:8][N:7]=[C:6](SC)[N:5]=1)([CH3:3])[CH3:2].[NH2:27][CH:28](O)[CH:29]([CH3:31])[CH3:30].C1C[O:36]CC1>CN1C(=O)CCC1>[OH:36][C:29]([CH3:31])([CH3:30])[CH2:28][NH:27][C:6]1[N:5]=[C:4]([CH:1]([CH3:3])[CH3:2])[C:9]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:17]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=3)[N:11]=2)=[CH:8][N:7]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 137974451-Amino-2-methylpropanol2×HCID 679837074-(4'-Isopropyl-2'-(methylthio)-4,5'-bipyrimidin-2-ylamino)benzonitrile

Product 1

HCID 680323414-(2'-(2-Hydroxy-2-methylpropylamino)-4'-isopropyl-4,5'-bipyrimidin-2-ylamino)benzonitrile

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-(4′-Isopropyl-2′-(methylthio)-4,5′-bipyrimidin-2-ylamino)benzonitrile (36b) (51.1 mg, 0.141 mmol) and 1-amino-2-methylpropanol (126 mg, 1.410 mmol) were dissolved in THF (513 μl) and NMP (51.3 μl), then the reaction mixture was microwaved at 200° C. for 2 hours. The reaction was approximately 10% complete. Additional 1-amino-2-methylpropanol (126 mg, 1.410 mmol) was added, and the reaction mixture was microwaved at 200° C. for an additional 2 hours. The reaction mixture was microwaved at 200° C. for additional 3.5 hours. The crude reaction mixture was purified by reverse-phase HPLC [30-100% organic phase over 15 minutes using 0.1% TFA modified mobile phase] to obtain the desired product as a yellow foamy solid. 1H NMR (400 MHz, MeOD) δ ppm 1.27 (d, J=6.57 Hz, 6H) 1.30 (s, 6H) 3.43-3.65 (m, 2H) 3.71 (ddd, J=13.52, 6.69, 6.57 Hz, 1H) 7.08 (d, J=5.05 Hz, 1H) 7.63 (m, J=9.09 Hz, 2H) 7.95 (m, J=8.59 Hz, 2H) 8.45 (s, 1H) 8.61 (d, J=5.05 Hz, 1H). HRMS (ES+) for C22H25N7O.H+ [MH+]: calcd, 404.2199; found, 404.2201. UV-LC: 95.41/100% UV purity at 214/254 nm; tR=5.73 minutes over 7.75 minutes.

Workup

  1. customthe reaction mixture was microwaved at 200° C. for an additional 2 hours
  2. customThe reaction mixture was microwaved at 200° C. for additional 3.5 hours
  3. customThe crude reaction mixture
  4. customwas purified by reverse-phase HPLC [30-100% organic phase over 15 minutes using 0.1% TFA modified mobile phase]

Sources & evidence

ORD record
ord-acbd5b51d1af4a23b57fc79c72a58a3d
Source dataset
uspto-grants-2014_04
Patent number
US08685993B2

Reaction notes

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