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

HRID 75332Notes

Reaction equation

HRID 75332 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]([NH2:28])[C:25]([C:29]#[N:30])=[C:24](Cl)[N:23]=1.C(N(C(C)C)C(C)C)C>C(#N)C>[NH2:21][C:22]1[N:27]=[C:26]([NH2:28])[C:25]([C:29]#[N:30])=[C:24]([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])[N:23]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86708006(1S)-1-(6-(3,5-Dimethylisoxazol-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamineHCID 867080212,4-Diamino-6-chloropyrimidine-5-carbonitrile

Product 1

HCID 730553982,4-Diamino-6-(((1S)-1-(6-(3,5-dimethylisoxazol-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrileYield 56.1%

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 (106 mg, 0.393 mmol), 2,4-diamino-6-chloropyrimidine-5-carbonitrile (100 mg, 0.590 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.205 mL, 1.179 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 35% ACN in water. The fractions containing the desired product were combined and concentrated in vacuo to give the title compound (89 mg, 56%). 1H NMR (500 MHz, CD3OD) δ ppm 1.36 (ddd, J=13.42, 6.59, 1.46 Hz, 3 H), 2.01 (d, J=1.46 Hz, 2 H), 2.15 (d, J=1.95 Hz, 1 H), 2.18-2.21 (m, 1 H), 2.32 (d, J=1.46 Hz, 2 H), 3.86 (d, J=1.46 Hz, 3 H), 5.38-5.49 (m, 1 H), 6.67 (dd, J=2.20, 1.22 Hz, 1H), 7.58 (dd, J=2.93, 1.46 Hz, 1 H), 7.69 (d, J=5.86 Hz, 1 H); ESI-MS m/z [M+H]+ calc'd for C20H21N9O, 404; found 404.

Workup

  1. concentrationconcentrated
  2. custompurified by preparative HPLC (basic mode)
  3. washeluting with 35% ACN in water
  4. additionThe fractions containing the desired product
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-611c1beae12c4d7382f14a2a6d6b2881
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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