Diisopropylethylamine → HCID 178516974, compound

HRID 707447Notes

Reaction equation

HRID 707447 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][N:15]=[C:10]3[N:9]([CH:16]3[CH2:18][CH2:17]3)[C:8]2=[O:19])[CH2:4]1.Cl[C:21]1[CH:30]=[CH:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][N:27]=2)[N:22]=1.C(N(CC)C(C)C)(C)C>CS(C)=O>[N:22]1[C:23]2[C:28](=[N:27][CH:26]=[CH:25][CH:24]=2)[CH:29]=[CH:30][C:21]=1[NH:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][N:15]=[C:10]3[N:9]([CH:16]3[CH2:17][CH2:18]3)[C:8]2=[O:19])[CH2:4]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 151530312-Chloro-1,5-naphthyridineHCID 178479284HCID 178479284, compound2×

Product 1

HCID 178516974HCID 178516974, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 1-(trans-3-aminocyclobutyl)-3-cyclopropyl-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride (Intermediate 79, 0.133 g, 0.472 mmol), 2-chloro-1,5-naphthyridine (0.100 g, 0.608 mmol) and DMSO (2 mL). N,N-Diisopropylethylamine (0.250 mL, 1.437 mmol) was added and the reaction mixture was sealed under argon and heated at 100° C. for 59 h. The reaction was cooled to room temperature and partitioned between water/DCM. The aqueous layer was extracted with DCM (3×) and the combined organic layers were evaporated onto silica gel and purified by flash chromatography (Isco, (25 gram)) eluting with 2M NH3 in MeOH:CH2Cl2 (0:1→1:19) to give 67 mg (34%) of a white crystalline solid. ESI-MS 374.0 [M+1]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.49 (dd, J=4.30, 1.56 Hz, 1 H), 8.00 (d, J=3.33 Hz, 1 H), 7.97 (d, J=3.33 Hz, 1 H), 7.93 (d, J=9.19 Hz, 1 H), 7.81-7.89 (m, 2 H), 7.46 (dd, J=8.41, 4.11 Hz, 1 H), 7.02 (d, J=9.19 Hz, 1 H), 5.21 (m, 1 H), 4.64-4.76 (m, 1 H), 3.25-3.38 (m, 2 H), 2.91-3.02 (m, 1 H), 2.34-2.45 (m, 2 H), 0.94-1.11 (m, 4 H)

Workup

  1. customA glass microwave reaction vessel
  2. customthe reaction mixture was sealed under argon
  3. temperatureThe reaction was cooled to room temperature
  4. custompartitioned between water/DCM
  5. extractionThe aqueous layer was extracted with DCM (3×)
  6. customthe combined organic layers were evaporated onto silica gel
  7. custompurified by flash chromatography (Isco, (25 gram))
  8. washeluting with 2M NH3 in MeOH:CH2Cl2 (0:1→1:19)

Sources & evidence

ORD record
ord-70938898710949f69c42ff2df104257d
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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