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

HRID 75334Notes

Reaction equation

HRID 75334 reaction equation
[F:1][CH:2]([F:21])[N:3]1[C:7]([C:8]2[CH:9]=[C:10]3[N:19]([CH3:20])[CH:18]=[CH:17][C:11]3=[N:12][C:13]=2[C@@H:14]([NH2:16])[CH3:15])=[CH:6][CH:5]=[N:4]1.[NH2:22][C:23]1[N:28]=[C:27](Cl)[C:26]([C:30]#[N:31])=[C:25](C)[N:24]=1.C([N:35](C(C)C)C(C)C)C>C(#N)C>[NH2:22][C:23]1[N:28]=[C:27]([NH2:35])[C:26]([C:30]#[N:31])=[C:25]([NH:16][C@H:14]([C:13]2[N:12]=[C:11]3[CH:17]=[CH:18][N:19]([CH3:20])[C:10]3=[CH:9][C:8]=2[C:7]2[N:3]([CH:2]([F:1])[F:21])[N:4]=[CH:5][CH:6]=2)[CH3:15])[N:24]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 754124462-Amino-4-chloro-6-methyl-5-pyrimidinecarbonitrileHCID 86707995(S)-1-(6-(1-(Difluoromethyl)-1H-pyrazol-5-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

Product 1

HCID 73055400(S)-2,4-Diamino-6-((1-(6-(1-(difluoromethyl)-1H-pyrazol-5-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrileYield 58.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

(S)-1-(6-(1-(Difluoromethyl)-1H-pyrazol-5-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (115 mg, 0.393 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 30-45% ACN in water. The fractions containing the desired compound were combined and extracted with EtOAc (200 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound (97 mg, 58%). 1H NMR (500 MHz, CD3OD) δ ppm 1.41-1.49 (m, 3 H), 3.88 (s, 3 H), 5.91 (q, J=6.67 Hz, 1 H), 6.63 (d, J=2.93 Hz, 1 H), 6.86 (d, J=2.44 Hz, 1 H), 7.49-7.77 (m, 2 H), 7.95 (s, 1 H), 8.19 (d, J=2.93 Hz, 1 H); ESI-MS m/z [M+H]+ calc'd for C19H18F2N10, 425; found 425.

Workup

  1. concentrationconcentrated
  2. custompurified by preparative HPLC (basic mode)
  3. washeluting with 30-45% ACN in water
  4. additionThe fractions containing the desired compound
  5. extractionextracted with EtOAc (200 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1f532b45fdfa41abae25c712c58bfab0
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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