Hydrochloric Acid → HCID 68459790, compound

HRID 2387488Notes

Reaction equation

HRID 2387488 reaction equation
[Cl:1]CCN1CCOCC1.[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][N:21]([C:24]2[CH:25]=[C:26]3[C:30](=[CH:31][CH:32]=2)[N:29]([CH2:33][CH:34]2[O:39][CH2:38][CH2:37][N:36](C(OC(C)(C)C)=O)[CH2:35]2)[N:28]=[CH:27]3)[C:20](=[O:47])[CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.FC(F)(F)C(O)=O.Cl>C(Cl)Cl.C(OCC)(=O)C.CCOCC>[ClH:1].[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][N:21]([C:24]2[CH:25]=[C:26]3[C:30](=[CH:31][CH:32]=2)[N:29]([CH2:33][CH:34]2[O:39][CH2:38][CH2:37][NH:36][CH2:35]2)[N:28]=[CH:27]3)[C:20](=[O:47])[CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 767274-(2-Chloroethyl)morpholineHCID 68460081HCID 68460081, compound

Product 1

HCID 68459790HCID 68459790, compoundYield 58%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Following the procedure of Example 2, but substituting tert-butyl 2-(bromomethyl)morpholine-4-carboxylate for 4-(2-chloroethyl)morpholine, tert-butyl 2-((5-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-1H-indazol-1-yl)methyl)morpholine-4-carboxylate (134 mg, 33%) was prepared as a white powder. A solution of this compound (134 mg, 0.26 mmol) in CH2Cl2 (1 mL) was treated with trifluoroacetic acid (148 mg, 1.3 mmol). After stirring at room temperature for 16 h, the reaction mixture was diluted with CH2Cl2 (50 mL) and washed with 1N NaOH (50 mL). The organics were dried (Na2SO4), filtered and concentrated. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH/NH4OH, 40:1:0.1 to 20:1.0.2) provided the free base. This was dissolved in ethyl acetate (0.3 mL) and treated with 1 equivalent of 1 M HCl in Et2O and the mixture was filtrated to provide the title compound (68.2 mg, 58%) as a yellow solid: melting point (mp) 221-223° C. dec; 1H NMR (500 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.18 (s, 1H), 7.75-7.70 (m, 2H), 7.62 (d, J=7.6 Hz, 1H), 7.49-7.40 (m, 4H), 7.39-7.35 (m, 2H), 6.11 (dd, J=7.6, 2.7 Hz, 1H), 5.99 (d, J=2.7 Hz, 1H), 5.15 (s, 2H), 4.64-4.60 (m, 2H), 4.20-4.15 (m, 1H), 3.93-3.88 (dd, J=12.6, 3.3 Hz, 1H), 3.68-3.60 (m, 1H), 3.36-3.32 (m, 1H), 3.15 (d, J=12.6 Hz, 1H), 2.96-2.84 (m, 2H); ESI MS m/z 417 [M+H]+.

Workup

  1. customwas prepared as a white powder
  2. washwashed with 1N NaOH (50 mL)
  3. dry with materialThe organics were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH/NH4OH, 40:1:0.1 to 20:1.0.2)
  7. customprovided the free base
  8. filtrationthe mixture was filtrated

Sources & evidence

ORD record
ord-8c24082190e64944b9730b6e5c347d7d
Source dataset
uspto-grants-2012_09
Patent number
US08268868B2

Reaction notes

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