Triethylamine → (3R)-1-[(4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl]-N-isopropylpyrrolidine-3-carboxamide

HRID 589120Notes

Reaction equation

HRID 589120 reaction equation
C(N(CC)CC)C.[CH:8]([NH:11][C:12]([C@@H:14]1[CH2:18][CH2:17][NH:16][CH2:15]1)=[O:13])([CH3:10])[CH3:9].Cl[C:20]1[N:28]2[C@@H:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=3)[CH2:30][O:31][C:26]3=[C:27]2[C:22](=[CH:23][CH:24]=[C:25]3[C:38]2[C:39]([CH3:44])=[N:40][O:41][C:42]=2[CH3:43])[N:21]=1>CN1CCCC1=O.CO>[CH3:44][C:39]1[C:38]([C:25]2[C:26]3[O:31][CH2:30][C@H:29]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=4)[N:28]4[C:20]([N:16]5[CH2:17][CH2:18][C@@H:14]([C:12]([NH:11][CH:8]([CH3:10])[CH3:9])=[O:13])[CH2:15]5)=[N:21][C:22]([C:27]=34)=[CH:23][CH:24]=2)=[C:42]([CH3:43])[O:41][N:40]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 67294089(3R)-N-Isopropylpyrrolidine-3-carboxamideHCID 90408898(4S)-2-Chloro-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine

Product 1

HCID 90408641(3R)-1-[(4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl]-N-isopropylpyrrolidine-3-carboxamideYield 10.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

Triethylamine (110 μL, 0.79 mmol) and (3R)—N-isopropylpyrrolidine-3-carboxamide (120 mg, 0.74 mmol) were added to a solution of (4S)-2-chloro-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine (66.0 mg, 0.18 mmol) in N-methylpyrrolidinone (1.5 mL), and the resulting mixture was heated in a microwave at 120° C. for 5 min. The mixture was diluted with methanol and purified twice by preparative LCMS using pH 10 buffer to give the title compound, (8.9 mg, 10%). LCMS calc. for C27H31N6O3 (M+H)+: m/z=487.2. found: 487.3. 1H NMR (500 MHz, DMSO) δ 8.54 (dd, J=4.8, 0.8 Hz, 1H), 7.79 (d, J=7.6 Hz, 1H), 7.72 (td, J=7.7, 1.8 Hz, 1H), 7.29 (dd, J=6.8, 4.9 Hz, 1H), 6.95 (d, J=8.1 Hz, 1H), 6.80 (d, J=8.1 Hz, 1H), 6.60 (d, J=7.9 Hz, 1H), 6.09 (t, 1H), 4.82 (dd, J=11.4, 1.3 Hz, 1H), 4.53 (dd, J=11.5, 2.8 Hz, 1H), 3.85-3.71 (m, 3H), 3.43 (dd, J=9.6, 7.6 Hz, 1H), 3.39-3.32 (m, 1H), 2.90 (p, J=7.8 Hz, 1H), 2.19 (s, 3H), 2.02 (s, 3H), 2.00-1.89 (m, 2H), 1.01 (dd, J=10.1, 6.6 Hz, 6H).

Workup

  1. custompurified twice by preparative LCMS

Sources & evidence

ORD record
ord-7cda0904cba64ad496c68ca5fce5db01
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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