Triethylamine → HCID 76287264, compound

HRID 1050322Notes

Reaction equation

HRID 1050322 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.C(N(CC)CC)C.[F:30][C:31]([F:42])([F:41])[C:32]1[CH:33]=[C:34]([CH:38]=[CH:39][CH:40]=1)[C:35](Cl)=[O:36]>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:35](=[O:36])[C:34]5[CH:38]=[CH:39][CH:40]=[C:32]([C:31]([F:30])([F:41])[F:42])[CH:33]=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 86723194HCID 86723194, compound

Product 1

HCID 76287264HCID 76287264, compoundYield 54.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

(8S,9aR)-8-[(5-Cyclopropylpyrazin-2-yl)oxy]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride (40 mg, 0.123 mmol, 1.0 equivalent, prepared as described in Example 46, Part H) was suspended in dichloromethane (1.0 mL) in a 4-mL scintillation vial, and triethylamine (0.051 mL, 0.37 mmol, 3.0 equivalents) was added. 3-(Trifluoromethyl)benzoyl chloride (33.4 mg, 0.160 mmol, 1.3 equivalents) was added as a solution in 0.1 mL of dichloromethane followed by 4-(dimethylamino)pyridine (1.50 mg, 0.012 mmol, 0.1 equivalent). The reaction was stirred for 30 minutes. The reaction solution was loaded directly onto a 4 g silica column and 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 (31 mg, 54%). 1H NMR (400 MHz, pyridine-d5, 90° C.) δ ppm 8.07 (d, J=1.3 Hz, 1H), 7.98 (d, J=1.3 Hz, 1H), 7.91 (s, 1H), 7.72 (d, J=7.7 Hz, 1H), 7.66 (d, J=7.8 Hz, 1H), 7.48 (t, J=7.8 Hz, 1H), 5.47 (t, J=4.4 Hz, 1H), 4.51 (s, 1H), 4.34 (dd, J=17.0, 9.1 Hz, 1H), 4.22 (d, J=13.6 Hz, 2H), 3.84-3.75 (m, 1H), 3.26 (dd, J=12.7, 11.1 Hz, 1H), 3.04 (dd, J=14.2, 9.5 Hz, 1H), 2.94-2.77 (m, 1H), 2.71 (dd, J=15.4, 4.9 Hz, 1H), 2.41 (dd, J=14.0, 6.7 Hz, 1H), 2.05-1.82 (m, 2H), 1.00 (dt, J=4.9, 2.9 Hz, 2H), 0.93-0.80 (m, 2H); MS (ESI+) m/z 461.1 (M+H)+; [α]D23.6=−0.09 (c=0.13, CH3OH).

Workup

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

Sources & evidence

ORD record
ord-fb4013bb720e48dc984ae658d00902d1
Source dataset
uspto-grants-2016_07
Patent number
US09382258B2

Reaction notes

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