Triethylamine → (8R,9aR)-8-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[3-(trifluoromethyl)benzoyl]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one

HRID 572046Notes

Reaction equation

HRID 572046 reaction equation
Cl.[CH:2]1([C:5]2[N:6]=[CH:7][C:8]([O:11][C@H:12]3[CH2:22][N:15]4[C:16](=[O:21])[CH2:17][CH2:18][NH:19][CH2:20][C@H:14]4[CH2:13]3)=[N:9][CH:10]=2)[CH2:4][CH2:3]1.[F:23][C:24]([F:35])([F:34])[C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=1)[C:28](Cl)=[O:29].C(N(CC)CC)C>ClCCl.CN(C)C1C=CN=CC=1>[CH:2]1([C:5]2[N:6]=[CH:7][C:8]([O:11][C@H:12]3[CH2:22][N:15]4[C:16](=[O:21])[CH2:17][CH2:18][N:19]([C:28](=[O:29])[C:27]5[CH:31]=[CH:32][CH:33]=[C:25]([C:24]([F:23])([F:34])[F:35])[CH:26]=5)[CH2:20][C@H:14]4[CH2:13]3)=[N:9][CH:10]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 752573-(Trifluoromethyl)benzoyl chlorideHCID 86723197(8R,9aR)-8-[(5-cyclopropylpyrazin-2-yl)oxy]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride

Product 1

HCID 76287559(8R,9aR)-8-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[3-(trifluoromethyl)benzoyl]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-oneYield 64%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

(8R,9aR)-8-[(5-Cyclopropylpyrazin-2-yl)oxy]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride (27.6 mg, 0.085 mmol, 1 equivalent, prepared as described in Example 55, Part B) was suspended in dichloromethane (1.0 mL) in a 4-mL scintillation vial. 3-(Trifluoromethyl)benzoyl chloride (23.05 mg, 0.111 mmol, 1.3 equivalents) was added as a solution in dichloromethane (0.1 mL) followed by the addition of triethylamine (0.059 mL, 0.425 mmol, 5.0 equiv) and 4-(dimethylamino)pyridine (1.0 mg, 0.0085 mmol, 0.1 equivalent). The resulting solution was stirred at room temperature for an additional 30 minutes. The reaction was loaded directly onto a 4 g silica gel column eluted with 50:50 to 100:0 ethyl acetate:heptanes (flow rate=18 mL/minute) over 20 minutes to give the title compound as a white solid (25 mg, 64%). 1H NMR (400 MHz, pyridine-d5, 90° C.) δ ppm 8.06 (s, 1H), 7.97 (d, J=1.3 Hz, 1H), 7.89 (s, 1H), 7.68 (dd, J=18.2, 7.8 Hz, 2H), 7.47 (t, J=7.8 Hz, 1H), 5.40 (dq, J=8.0, 4.0 Hz, 1H), 4.53-4.10 (m, 1H), 4.13 (td, J=8.8, 3.6 Hz, 2H), 3.96 (d, J=4.1 Hz, 2H), 3.41 (dd, J=13.9, 10.0 Hz, 1H), 3.32-3.17 (m, 1H), 2.90-2.67 (m, 2H), 2.55 (ddd, J=14.2, 8.8, 5.5 Hz, 1H), 2.07-1.91 (m, 2H), 1.06-0.97 (m, 2H), 0.92-0.79 (m, 2H); MS (ESI+) m/z 461.1 (M+H)+; [α]D23.7=0.10 (c=0.12, CH3OH).

Workup

  1. washeluted with 50:50 to 100:0 ethyl acetate

Sources & evidence

ORD record
ord-f8b11efea55e4f1aa243d2bccd75385b
Source dataset
uspto-grants-2015_05
Patent number
US09029361B2

Reaction notes

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