Water → HCID 73331075, compound

HRID 1055270Notes

Reaction equation

HRID 1055270 reaction equation
[F:1][C:2]1[CH:44]=[CH:43][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][C:17]4[C:22](=[O:23])[N:21]5[CH2:24][CH2:25][CH2:26][CH:27]([O:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][C:34](=[O:41])[N:35]6[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]6)[C:20]5=[N:19][C:18]=4[CH3:42])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[C:45]1(=[O:51])[O:50][C:48](=[O:49])[CH2:47][CH2:46]1.C(N(C(C)C)CC)(C)C.O>ClCCl>[F:1][C:2]1[CH:44]=[CH:43][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][C:17]4[C:22](=[O:23])[N:21]5[CH2:24][CH2:25][CH2:26][CH:27]([O:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][C:34]([N:35]6[CH2:40][CH2:39][N:38]([C:45](=[O:51])[CH2:46][CH2:47][C:48]([OH:50])=[O:49])[CH2:37][CH2:36]6)=[O:41])[C:20]5=[N:19][C:18]=4[CH3:42])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7922Succinic anhydrideHCID 81531DiisopropylethylamineHCID 86711159HCID 86711159, compound

Product 1

HCID 73331075HCID 73331075, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-(2-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-2-methyl-9-((6-oxo-6-(piperazin-1-yl)hexyl)oxy)-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one, prepared as described in Step B, (239 mg, 0.39 mmol) in dichloromethane (5 mL), under argon, was treated with succinic anhydride (43.15 mg, 0.43 mmol) and diisopropylethylamine (68.35 μL, 0.39 mmol). After stirring for 2 h at room temperature, the reaction mixture was poured into water (5 mL), and the aqueous layer was extracted with dichloromethane/methanol (95/5, three times 5 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by HPLC and triturated with diisopropylether, to give the title compound. (ESI-MS (M+1) 709); 1H NMR: (CDCl3, 360 MHz): δ ppm 1.10-2.80 (m, 31H), δ 3.20-4.00 (m, 13H), δ 4.24-4.30 (m, 1H), δ 7.07 (td, J=8.97, 1.83 Hz, 1H), δ 7.24 (d, J=1.83 Hz, 1H), δ 7.76 (dd, J=8.60, 4.94 Hz, 1H)

Workup

  1. extractionthe aqueous layer was extracted with dichloromethane/methanol (95/5, three times 5 mL)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by HPLC
  6. customtriturated with diisopropylether

Sources & evidence

ORD record
ord-1b949e5903154460bf6d5f279cb2a99f
Source dataset
uspto-grants-2016_07
Patent number
US09394354B2

Reaction notes

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