Acetyl chloride → (R)-10-(1-acetyl-3-methyl-azetidin-3-yl)-1-methyl-3,5-dihydro-10H-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-2-one

HRID 519141Notes

Reaction equation

HRID 519141 reaction equation
Cl.[CH3:2][C@@H:3]1[C:16](=[O:17])[NH:15][N:14]=[C:13]2[N:4]1[C:5]1[CH:6]=[C:7]3[N:20]([C:21]4([CH3:25])[CH2:24][NH:23][CH2:22]4)[CH:19]=[CH:18][C:8]3=[CH:9][C:10]=1[O:11][CH2:12]2.[C:26](Cl)(=[O:28])[CH3:27]>C(Cl)Cl>[C:26]([N:23]1[CH2:22][C:21]([N:20]2[C:7]3[C:8](=[CH:9][C:10]4[O:11][CH2:12][C:13]5[N:4]([C:5]=4[CH:6]=3)[C@H:3]([CH3:2])[C:16](=[O:17])[NH:15][N:14]=5)[CH:18]=[CH:19]2)([CH3:25])[CH2:24]1)(=[O:28])[CH3:27]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 86727525(R)-1-methyl-10-(3-methyl-azetidin-3-yl)-3,5-dihydro-10H-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-2-one hydrochloride

Product 1

HCID 86727533(R)-10-(1-acetyl-3-methyl-azetidin-3-yl)-1-methyl-3,5-dihydro-10H-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-2-oneYield 33.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of (R)-1-methyl-10-(3-methyl-azetidin-3-yl)-3,5-dihydro-10H-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-2-one hydrochloric acid (Example #148, 0.4 g, 1.2 mmol) in DCM (15 mL) was added acetyl chloride (0.42 g, 5.35 mmol) and TEA (0.37 g, 3.69 mmol) at 0° C. The reaction mixture was stirred at ambient temperature for 1 h. The mixture was concentrated in vacuo and the residue was purified by prep-HPLC (Table 3, Method 29) to give (R)-10-(1-acetyl-3-methyl-azetidin-3-yl)-1-methyl-3,5-dihydro-10H-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-2-one (0.146 g, 11%) as a pale yellow solid. 1H NMR (400 MHz, methanol-d4): δ 7.27 (s, 1H), 7.21 (s, 1H), 6.87 (d, J=10.8 Hz, 1H), 6.45 (s, 1H), 5.04 (m, 1H), 4.90 (m, 1H), 4.61 (m, 4H), 4.34 (m, 1H), 2.04 (m, 3H), 1.79 (m, 3H), 1.44 (m, 3H). LC/MS (Table 1, Method 4) Rt=1.836 min.; MS m/z: 368 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue was purified by prep-HPLC (Table 3, Method 29)

Sources & evidence

ORD record
ord-8e93644d09d7405c8eb949863713890e
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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