Diisopropylethylamine → HCID 178510648, compound

HRID 707367Notes

Reaction equation

HRID 707367 reaction equation
[CH:1]1([N:4]2[C:12]3[C:7](=[N:8][CH:9]=[CH:10][N:11]=3)[N:6]([C@H:13]3[CH2:16][C@H:15]([NH:17][C:18]4[S:19][C:20]([C:23](O)=[O:24])=[CH:21][N:22]=4)[CH2:14]3)[C:5]2=[O:26])[CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.[N:34]1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)[C:38]2C=C[CH:41]=[CH:42][C:37]=2[N:36]=N1.C(N(C(C)C)CC)(C)C.Cl.NC1(C#N)CC1>C(Cl)Cl>[C:38]([C:37]1([NH:36][C:23]([C:20]2[S:19][C:18]([NH:17][C@H:15]3[CH2:16][C@H:13]([N:6]4[C:7]5=[N:8][CH:9]=[CH:10][N:11]=[C:12]5[N:4]([CH:1]5[CH2:2][CH2:3]5)[C:5]4=[O:26])[CH2:14]3)=[N:22][CH:21]=2)=[O:24])[CH2:41][CH2:42]1)#[N:34]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 145863631-Amino-1-cyclopropanecarbonitrile hydrochlorideHCID 178524766HCID 178524766, compound

Product 1

HCID 178510648HCID 178510648, compoundYield 73.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-((trans-3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-1-yl)cyclobutyl)amino)thiazole-5-carboxylic acid, (EXAMPLE 149), (0.070 g, 0.188 mmol), (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (0.147 g, 0.282 mmol), diisopropylethylamine (0.049 ml, 0.282 mmol), and 1-amino-1-cyclopropanecarbonitrile hydrochloride (0.033 g, 0.282 mmol) in DCM (5 mL) was stirred at room temperature for 12 hours. Purification of the reaction mixture using silica chromatography with ISCO eluting with 0-80% EtOAc/hexanes gave the title compound N-(1-cyanocyclopropyl)-2-((trans-3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-1-yl)cyclobutyl)amino)thiazole-5-carboxamide (0.060 g, 0.137 mmol, 73.1% yield). m/z: 437 (M+1); 1H NMR (400 MHz, DMSO-d6) δ: ppm 8.78 (s, 1 H) 8.32 (d, J=6.65 Hz, 1 H) 7.93-8.05 (m, 2 H) 7.40 (s, 1 H) 5.18 (quin, J=8.51 Hz, 1 H) 4.31-4.53 (m, 1 H) 3.21-3.41 (m, 2 H) 2.88-3.05 (m, 1 H) 2.29-2.44 (m, 2 H) 1.44-1.60 (m, 2 H) 1.23-1.35 (m, 2 H) 0.93-1.10 (m, 4 H).

Workup

  1. customPurification of the reaction mixture
  2. washeluting with 0-80% EtOAc/hexanes

Sources & evidence

ORD record
ord-71274979831845479c82a195433d2cb9
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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