Diisopropylethylamine → 2-Amino-4-(((1S)-1-(6-(3,5-dimethylisoxazol-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-6-methylpyrimidine-5-carbonitrile

HRID 75333Notes

Reaction equation

HRID 75333 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[N:18]([CH3:19])[CH:17]=[CH:16][C:10]3=[N:11][C:12]=2[C@@H:13]([NH2:15])[CH3:14])=[C:5]([CH3:20])[O:4][N:3]=1.[NH2:21][C:22]1[N:27]=[C:26](Cl)[C:25]([C:29]#[N:30])=[C:24]([CH3:31])[N:23]=1.C(N(C(C)C)C(C)C)C>C(#N)C>[NH2:21][C:22]1[N:27]=[C:26]([NH:15][C@H:13]([C:12]2[N:11]=[C:10]3[CH:16]=[CH:17][N:18]([CH3:19])[C:9]3=[CH:8][C:7]=2[C:6]2[C:2]([CH3:1])=[N:3][O:4][C:5]=2[CH3:20])[CH3:14])[C:25]([C:29]#[N:30])=[C:24]([CH3:31])[N:23]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 754124462-Amino-4-chloro-6-methyl-5-pyrimidinecarbonitrileHCID 86708006(1S)-1-(6-(3,5-Dimethylisoxazol-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

Product 1

HCID 730553992-Amino-4-(((1S)-1-(6-(3,5-dimethylisoxazol-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-6-methylpyrimidine-5-carbonitrileYield 39%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

(1S)-1-(6-(3,5-Dimethylisoxazol-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (107 mg, 0.395 mmol), 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (100 mg, 0.593 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.21 mL, 1.2 mmol) were combined in acetonitrile (6 mL). The reaction mixture was heated in a microwave reactor at 120° C. for 2 hours and then concentrated. The residue was taken up in DMF and purified by preparative HPLC (basic mode) eluting with 45% ACN in water. The fractions containing the desired product were combined and concentrated in vacuo to give the title compound (62 mg, 39%). 1H NMR (500 MHz, CD3OD) δ ppm 1.31-1.42 (m, 3 H), 2.01 (s, 2 H), 2.15 (s, 1 H), 2.19 (s, 1 H), 2.32 (d, J=4.39 Hz, 5 H), 3.86 (s, 3 H), 5.39-5.48 (m, 1 H), 6.65-6.69 (m, 1H), 7.59 (d, J=3.42 Hz, 1 H), 7.68-7.73 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C2H22N8O, 403; found 403.

Workup

  1. concentrationconcentrated
  2. custompurified by preparative HPLC (basic mode)
  3. washeluting with 45% ACN in water
  4. additionThe fractions containing the desired product
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-57dd7a02d9d246a2aecb8ec3379242d5
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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