Diisopropylethylamine → HCID 178429379, compound

HRID 707383

Reaction equation

HRID 707383 reaction equation
Cl.Cl.[NH2:3][C@H:4]1[CH2:7][C@H:6]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][N:16]=[C:11]3[C:10]([CH3:18])([CH3:17])[C:9]2=[O:19])[CH2:5]1.C(N(C(C)C)C(C)C)C.CS([C:33]1[S:34][C:35]2[C:40]([N:41]=1)=[CH:39][CH:38]=[CH:37][N:36]=2)(=O)=O>CS(C)=O.CCOC(C)=O.O>[CH3:18][C:10]1([CH3:17])[C:11]2[C:12](=[N:13][CH:14]=[CH:15][N:16]=2)[N:8]([C@H:6]2[CH2:7][C@H:4]([NH:3][C:33]3[S:34][C:35]4[C:40]([N:41]=3)=[CH:39][CH:38]=[CH:37][N:36]=4)[CH2:5]2)[C:9]1=[O:19]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 36045032-(Methylsulfonyl)thiazolo[5,4-b]pyridine2×HCID 178429369HCID 178429369, compound2×

Product 1

HCID 178429379HCID 178429379, compoundYield 60.5%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-(trans-3-aminocyclobutyl)-7,7-dimethyl-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one dihydrochloride (Intermediate 83, 51 mg, 0.167 mmol), N-ethyl-N-isopropylpropan-2-amine (102 μl, 0.585 mmol), and 2-(methylsulfonyl)thiazolo[5,4-b]pyridine (Intermediate 76) (43.0 mg, 0.201 mmol) in DMSO (0.3 ml) was stirred at 100° C. for 3 h. The mixture was diluted with EtOAc and water in a separatory funnel. The aqueous layer was extracted with EtOAc twice. The combined organic layer was dried over Na2SO4 and concentrated in vacuo. The crude solution was purified by silica gel chromatography (ISCO 12 g, 0-70% EtOAc-hexane) to give 7,7-dimethyl-5-(trans-3-(thiazolo[5,4-b]pyridin-2-ylamino)cyclobutyl)-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one (37 mg, 0.101 mmol, 60.4% yield) as off-white solid. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.46 (s, 6 H) 2.50 (ddd, J=14.03, 9.35, 3.51 Hz, 2 H) 3.37-3.55 (m, 2 H) 5.30 (t, J=8.48 Hz, 1 H) 5.73 (br. s., 1 H) 7.17-7.25 (m, 1 H) 7.74 (dd, J=8.04, 1.46 Hz, 1 H) 8.05-8.16 (m, 2 H) 8.22 (dd, J=4.75, 1.53 Hz, 1 H).

Workup

  1. extractionThe aqueous layer was extracted with EtOAc twice
  2. dry with materialThe combined organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe crude solution was purified by silica gel chromatography (ISCO 12 g, 0-70% EtOAc-hexane)

Sources & evidence

ORD record
ord-cba2053e67e34362bcc5567ab35ee0e6
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Linked notes

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