Acetyl chloride → 1-(6-Acetyl-9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridin-2-yl)-4-(benzyloxy)pyridin-2(1H)-one

HRID 882045Notes

Reaction equation

HRID 882045 reaction equation
C(N(CC)CC)C.[C:8](Cl)(=[O:10])[CH3:9].[CH2:12]([O:19][C:20]1[CH:25]=[CH:24][N:23]([C:26]2[N:31]=[C:30]3[N:32]([CH3:39])[C:33]4[CH2:38][CH2:37][NH:36][CH2:35][C:34]=4[C:29]3=[CH:28][CH:27]=2)[C:22](=[O:40])[CH:21]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:8]([N:36]1[CH2:37][CH2:38][C:33]2[N:32]([CH3:39])[C:30]3[C:29]([C:34]=2[CH2:35]1)=[CH:28][CH:27]=[C:26]([N:23]1[CH:24]=[CH:25][C:20]([O:19][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[CH:21][C:22]1=[O:40])[N:31]=3)(=[O:10])[CH3:9]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 575245054-(Benzyloxy)-1-(9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridin-2-yl)pyridin-2(1H)-one

Product 1

HCID 575245871-(6-Acetyl-9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridin-2-yl)-4-(benzyloxy)pyridin-2(1H)-oneYield 83.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Triethylamine (33 μL, 0.24 mmol), DMAP (5.8 mg, 0.048 mmol) and acetyl chloride (25 μL, 0.36 mmol) were added to a solution of 4-(benzyloxy)-1-(9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3′,4′:4,5]pyrrolo[2,3-b]pyridin-2-yl)pyridin-2(1H)-one (93 mg, 0.24 mmol) in CH2Cl2 (14 mL) and the resulting solution was stirred at ambient temperature for 2 h under N2. The resulting solution was concentrated to dryness under reduced pressure. Flash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 2 column volumes, increased to 0:100 over 20 column volumes and held for 5 column volumes) gave the title compound (86 mg, 83%) as an off-white powder and a mixture of rotomers: mp 206-208° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.01 (t, J=8.5 Hz, 1H), 7.80 (dd, J=7.5, 2.5 Hz, 1H), 7.49-7.36 (m, 5H), 7.33-7.26 (m, 1H), 6.15 (dd, J=8.0, 3.0 Hz, 1H), 5.98 (d, J=2.5 Hz, 1H), 5.16 (s, 2H), 4.71-4.66 (m, 2H), 3.90-3.81 (m, 2H), 3.67 (m, 3H), 3.00-2.86 (m, 2H), 2.16-2.10 (m, 3H); ESI MS m/z 429 [M+H]; HPLC (Method A)>99% (AUC), tR=18.2 min.

Workup

  1. concentrationThe resulting solution was concentrated to dryness under reduced pressure
  2. temperatureFlash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 2 column volumes, increased to 0:100 over 20 column volumes and held for 5 column volumes)

Sources & evidence

ORD record
ord-077c58b1d41b46dda52c4df6c1622994
Source dataset
uspto-grants-2015_03
Patent number
US08993765B2

Reaction notes

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