Diisopropylethylamine → HCID 178461980, compound

HRID 75322Notes

Reaction equation

HRID 75322 reaction equation
Cl.C([O:9][C:10]1[CH:15]=[C:14]([C:16]2[CH:17]=[C:18]3[N:27]([CH3:28])[CH:26]=[CH:25][C:19]3=[N:20][C:21]=2[C@@H:22]([NH2:24])[CH3:23])[CH:13]=[CH:12][N:11]=1)C1C=CC=CC=1.Cl.N[C@H](C1N=C2C=CN(C)C2=CC=1C1C=CN=C(O)C=1)C.[NH2:50][C:51]1[N:56]=[C:55]([NH2:57])[C:54]([C:58]#[N:59])=[C:53](Cl)[N:52]=1.C(N(C(C)C)C(C)C)C>C(#N)C>[NH2:50][C:51]1[N:56]=[C:55]([NH2:57])[C:54]([C:58]#[N:59])=[C:53]([NH:24][C@H:22]([C:21]2[N:20]=[C:19]3[CH:25]=[CH:26][N:27]([CH3:28])[C:18]3=[CH:17][C:16]=2[C:14]2[CH:13]=[CH:12][N:11]=[C:10]([OH:9])[CH:15]=2)[CH3:23])[N:52]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 867080212,4-Diamino-6-chloropyrimidine-5-carbonitrileHCID 86708023(S)-1-(6-(2-(benzyloxy)pyridin-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine hydrochlorideHCID 178461863HCID 178461863, compound

Product 1

HCID 178461980HCID 178461980, compoundYield 46.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (S)-1-(6-(2-(benzyloxy)pyridin-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine hydrochloride (155 mg, 0.393 mmol) and (S)-4-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)pyridin-2-ol hydrochloride (120 mg, 0.393 mmol) along with 2,4-diamino-6-chloropyrimidine-5-carbonitrile (100 mg, 0.590 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.205 mL, 1.18 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 dissolved in MeOH (10 mL). Pd/C (10%, 700 mg) was added and the reaction mixture was maintained under an atmosphere of hydrogen for 30 minutes. The mixture was filtered through Celite and concentrated. The residue was taken up in DMF and purified by preparative HPLC (basic mode) eluting with 20-35% ACN in water. The fractions containing the desired product were combined and concentrated in vacuo to give the title compound (73 mg, 46%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.22-1.32 (m, 3 H), 3.80 (br s, 3 H), 5.58 (quin, J=6.71 Hz, 1 H), 6.31 (d, J=6.83 Hz, 1 H), 6.48 (br s, 2 H), 6.52-6.63 (m, 5 H), 6.66 (d, J=7.81 Hz, 1 H), 7.52 (d, J=6.35 Hz, 1 H), 7.72 (d, J=2.93 Hz, 1 H), 7.80 (s, 1 H); ESI-MS m/z [M+H]+ calc'd for C20H19N9O, 402; found 402.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in MeOH (10 mL)
  3. additionPd/C (10%, 700 mg) was added
  4. temperaturethe reaction mixture was maintained under an atmosphere of hydrogen for 30 minutes
  5. filtrationThe mixture was filtered through Celite
  6. concentrationconcentrated
  7. custompurified by preparative HPLC (basic mode)
  8. washeluting with 20-35% ACN in water
  9. additionThe fractions containing the desired product
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bd34a423c8034c0eba52f025ad0a625a
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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