1-Phenylcyclopropanecarboxylic acid → HCID 57737254, compound

HRID 1157644Notes

Reaction equation

HRID 1157644 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:18]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([NH:25][C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH2:33][CH2:34][N:35]([CH3:37])[CH3:36])[CH:27]=4)[N:20]=3)=[C:11]3[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:38]1([C:44]2([C:47](O)=[O:48])[CH2:46][CH2:45]2)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[CH3:37][N:35]([CH3:36])[CH2:34][CH2:33][O:32][C:28]1[CH:27]=[C:26]([NH:25][C:21]2[N:20]=[C:19]([C:18]3[C:8]([C:4]4[CH:3]=[C:2]([NH:1][C:47]([C:44]5([C:38]6[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=6)[CH2:46][CH2:45]5)=[O:48])[CH:7]=[CH:6][CH:5]=4)=[N:9][N:10]4[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=34)[CH:24]=[CH:23][N:22]=2)[CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 802061-Phenylcyclopropanecarboxylic acid2×HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 57737217HCID 57737217, compound

Product 1

HCID 57737254HCID 57737254, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-[2-(3-Aminophenyl)-6-(methyloxy)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-{[2-(dimethylamino)ethyl]oxy}phenyl)-2-pyrimidinamine (100 mg, 0.21 mmol), 1-phenylcyclopropanecarboxylic acid (41 mg, 0.25 mmol), and diisopropylethylamine (0.10 mL, 1.0 mmol) were combined in DMF (1 mL) followed by the addition of HATU [O-(7-azabenzotriazole-1 yloxy)tripyrrolidinophosphonium hexafluorophosphate] (78 mg, 0.21 mmol). The mixture was stirred for 2 h at rt after which time additional HATU (80 mg, 0.21 mmol), 1-phenylcyclopropanecarboxylic acid (40 mg, 0.25 mmol), and diisopropylethylamine (0.10 mL, 1.0 mmol) were added. The mixture was stirred for 16 h after which time the mixture was poured into water, extracted with DCM, and the organic phase concentrated and purified by silica get chromatography to afford the title compound as a yellow solid (55 mg, 41%). 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.24 (s, 1H), 8.53 (d, J=2.1 Hz, 1H), 8.43 (d, J=10.4 Hz, 1H), 8.20 (d, J=5.2 Hz, 1H), 7.85 (br s, 1H), 7.66 (d, J=8.3 Hz, 1H), 7.52 (br s, 1H), 7.39-7.31 (m, 5H), 7.28-7.20 (m, 4H), 7.13 (t, J=8.1 Hz, 1H), 6.51 (dd, J=7.9, 2.3 Hz, 1H), 6.43 (d, J=5.2 Hz, 1H), 3.97 (t, J=6.5 Hz, 2H), 3.86 (s, 3H), 2.65-2.60 (m, 2H), 2.20 (s, 6H), 1.42 (m, 2H), 1.09 (m, 2H). ES-LC/MS m/z=640 [M+H]+.

Workup

  1. additionwere added
  2. extractionextracted with DCM
  3. concentrationthe organic phase concentrated
  4. custompurified by silica
  5. customget chromatography

Sources & evidence

ORD record
ord-2f958914d49e4c3d81cdf07991afe144
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

Loading…