Hydrochloric Acid → HCID 71610212, compound

HRID 1479062Notes

Reaction equation

HRID 1479062 reaction equation
Cl.C(OC([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH:10]1[CH2:15][O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]([N:25]1[CH2:39][C:28]2=[C:29]3[N:34]([N:35]=[C:27]2[CH2:26]1)[C:33]([CH3:36])=[C:32]([Cl:37])[C:31]([CH3:38])=[N:30]3)=[O:24])=O)(C)(C)C.O>O1CCOCC1>[Cl:37][C:32]1[C:31]([CH3:38])=[N:30][C:29]2[N:34]([N:35]=[C:27]3[CH2:26][N:25]([C:23]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=4[O:16][CH2:15][CH:10]4[CH2:11][O:12][CH2:13][CH2:14][NH:9]4)=[O:24])[CH2:39][C:28]3=2)[C:33]=1[CH3:36]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 131736545HCID 131736545, compound

Product 1

HCID 71610212HCID 71610212, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A 4M solution of HCl in 1,4-dioxane (3.2 mL; 12.7 mmol; 10 eq.) was added to a suspension of 3-[2-(6-chloro-5,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carbonyl)-phenoxymethyl]-morpholine-4-carboxylic acid tert-butyl ester (690 mg; 1.27 mmol; 1 eq.) in 1,4-dioxane (10 mL) followed by WATER (130 μL) and the resulting mixture was stirred at room temperature for 16 hours. After concentration in vacuo, the residue was partitioned between DCM and 1M NaOH and the aqueous layer was extracted with DCM. The combined organic phase was dried over sodium sulfate and concentrated in vacuo. Crystallization from EA afforded the title compound (240 mg, 43%) as a yellow solid. 1H NMR (CDCl3) δ 7.44-7.30 (m, 2H), 7.13-7.01 (m, 1H), 6.96 (dd, J=8.2, 4.0 Hz, 1H), 5.07-4.96 (m, 2H), 4.68-4.55 (m, 2H), 4.03-3.89 (m, 2H), 3.85-3.76 (m, 1H), 3.76-3.66 (m, 1H), 3.51-3.39 (m, 1H), 3.31 (t, J=10.0 Hz, 1H), 3.25-3.12 (m, 1H), 2.95-2.76 (m, 5H), 2.69 (s, 1.1H), 2.61 (s, 1.9H), 1.94 (brs, 1H). HPLC (max plot) 94.4%, Rt 2.72 min. UPLC/MS: (MS+) 442.5 ([M+H]+).

Workup

  1. concentrationAfter concentration in vacuo
  2. customthe residue was partitioned between DCM and 1M NaOH
  3. extractionthe aqueous layer was extracted with DCM
  4. dry with materialThe combined organic phase was dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customCrystallization from EA

Sources & evidence

ORD record
ord-59d102c05fa543b49ba607a84a85bce9
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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