Hydrochloric Acid → HCID 68458454, compound

HRID 2387490Notes

Reaction equation

HRID 2387490 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][C@H:34]2[CH2:38][CH2:37][CH2:36][N:35]2C(OC(C)(C)C)=O)[N:28]=[CH:27]3)[C:20](=[O:46])[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.CCOC(C)=O.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][C@H:34]2[CH2:38][CH2:37][CH2:36][NH:35]2)[N:28]=[CH:27]3)[C:20](=[O:46])[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 68460564HCID 68460564, compound

Product 1

HCID 68458454HCID 68458454, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Following the procedure of Example 2, but substituting (R)-tert-butyl 2-(bromomethyl)pyrrolidine-1-carboxylate for 4-(2-chloroethyl)morpholine, (R)-tert-butyl 2-((5-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-1H-indazol-1-yl)methyl)pyrrolidine-1-carboxylate (22 mg, 8%) was prepared as a yellow powder. A solution of this compound (22 mg, 0.044 mmol) in CH2Cl2 (2 mL) was treated with trifluoroacetic acid (25 mg, 0.22 mmol). After stirring at room temperature for 16 h, the reaction mixture was diluted with EtOAc (10 mL) and washed with 1N NaOH (10 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 (0.4 mL) and treated with 1 equivalent of 1 M HCl in Et2O and the mixture was filtered to provide the title compound (14.8 mg, 77%) as a yellow solid: 1H NMR (500 MHz, DMSO-d6) δ 9.25 (s, 1H), 9.01 (s, 1H), 8.25 (s, 1H), 7.86 (d, J=8.9 Hz, 1H), 7.79 (d, J=17 Hz, 1H), 7.60 (d, J=7.6 Hz, 1H), 7.49-7.35 (m, 6H), 6.12 (dd, J=7.6, 2.6 Hz, 1H), 5.99 (d, J=2.7 Hz, 1H), 5.16 (s, 2H), 4.85-4.71 (m, 2H), 4.02-3.92 (m, 1H), 3.32-3.22 (m, 1H), 3.20-3.11 (m, 1H), 2.14-2.05 (m, 1H), 2.02-1.92 (m, 1H), 1.91-1.85 (m, 1H), 1.78-1.68 (m, 1H); ESI MS m/z 401 [M+H]+.

Workup

  1. customwas prepared as a yellow powder
  2. washwashed with 1N NaOH (10 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 filtered

Sources & evidence

ORD record
ord-56f6671a2a6648a48afa673cbdf62801
Source dataset
uspto-grants-2012_09
Patent number
US08268868B2

Reaction notes

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