1-Amino-2-propanol → 4-(4'-Ethyl-2'-(2-hydroxy-2-methylpropylamino)-4,5'-bipyrimidin-2-ylamino)benzonitrile

HRID 2359777Notes

Reaction equation

HRID 2359777 reaction equation
[CH2:1]([C:3]1[C:8]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)[N:10]=2)=[CH:7][N:6]=[C:5](SC)[N:4]=1)[CH3:2].[NH2:26][CH2:27][CH:28]([OH:30])[CH3:29].N[CH:32](O)C(C)C>C1COCC1.CN1C(=O)CCC1>[CH2:1]([C:3]1[C:8]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)[N:10]=2)=[CH:7][N:6]=[C:5]([NH:26][CH2:27][C:28]([OH:30])([CH3:32])[CH3:29])[N:4]=1)[CH3:2]

Participants

6

Reactant 3

HCID 41-Amino-2-propanolHCID 137974451-Amino-2-methylpropanol2×HCID 679838474-(4'-Ethyl-2'-(methylthio)-4,5'-bipyrimidin-2-ylamino)benzonitrile

Product 1

HCID 679839924-(4'-Ethyl-2'-(2-hydroxy-2-methylpropylamino)-4,5'-bipyrimidin-2-ylamino)benzonitrileYield 9.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-(4′-Ethyl-2′-(methylthio)-4,5′-bipyrimidin-2-ylamino)benzonitrile (36a) (48.6 mg, 0.112 mmol) and 1-amino-2-propanol (29.8 mg, 0.335 mmol) were dissolved in THF (540 μl) and NMP (54.0 μl), then the reaction mixture was microwaved at 150° C. for 1 hour. Additional 1-amino-2-methylpropanol (99.8 mg, 1.12 mmol) was added, and the reaction mixture was microwaved further at 150° C. an additional 1 hour. Additional 1-amino-2-methylpropanol (99.8 mg, 1.12 mmol) was added, and the reaction mixture was microwaved further at 200° C. The crude reaction mixture was purified by reverse-phase HPLC [30-100% organic phase over 15 minutes using 0.1% TFA modifier] followed by Biotage™ silica gel chromatography [10 g SNAP column, 100% DCM to 10% MeOH/DCM] to obtain the desired product as a pale yellow solid (4.14 mg, 9% yield). 1H NMR (400 MHz, MeOD) δ ppm 1.20-1.27 (m, 9H) 2.94 (q, J=7.58 Hz, 2H) 3.51 (s, 2H) 4.55 (s, 1H) 7.04 (d, J=5.56 Hz, 1H) 7.62 (m, J=9.09 Hz, 2H) 7.96 (m, J=8.59 Hz, 2H) 8.44 (s, 1H) 8.52 (d, J=5.05 Hz, 1H). HRMS (ES+) for C21H23N7O.H+ [MH+]: calcd, 390.2042; found, 390.2023. UV-LC: 96.40/95.08% UV purity at 214/254 nm; tR=5.31 minutes over 7.75 minutes.

Workup

  1. customthe reaction mixture was microwaved further at 150° C. an additional 1 hour
  2. customthe reaction mixture was microwaved further at 200° C
  3. customThe crude reaction mixture
  4. customwas purified by reverse-phase HPLC [30-100% organic phase over 15 minutes using 0.1% TFA modifier]

Sources & evidence

ORD record
ord-66690b2b8a574672b9709cba035c65cb
Source dataset
uspto-grants-2014_04
Patent number
US08685993B2

Reaction notes

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