Water → HCID 66823764, compound

HRID 1909949Notes

Reaction equation

HRID 1909949 reaction equation
[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[N:16]([C:20](=[O:28])[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:15][CH2:14]4)=[CH:9][S:10][C:6]=2[C:5]([C:29]2[CH2:30][CH2:31][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:33][CH:34]=2)=[CH:4][N:3]=1.CC1C=C2N=C3C(=NC(NC3=O)=O)N(C[C@H](O)[C@H](O)[C@H](O)CO)C2=CC=1C.O.O1CCCC1>C(O)C.[Pd]>[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[N:16]([C:20](=[O:28])[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:15][CH2:14]4)=[CH:9][S:10][C:6]=2[C:5]([CH:29]2[CH2:30][CH2:31][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:33][CH2:34]2)=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 493570RiboflavinHCID 66823627HCID 66823627, compound

Product 1

HCID 66823764HCID 66823764, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A suspension of 1,1-dimethylethyl 4-{4-amino-3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-7-yl}-3,6-dihydro-1(2H)-pyridinecarboxylate (220 mg, 0.388 mmol) and Pd/C, 10 wt. % (dry basis), wet, Degussa type E101 NE/W, ca. 50% water (25 mg, 0.012 mmol) in Ethanol (10 mL) was stirred under an atmosphere of hydrogen for 2 hours. The starting material never seemed to go into solution (the mixture was a thick gray suspension), so Tetrahydrofuran (THF) (15 mL) was added. It was stirred under hydrogen for another 17 hr, then filtered. LCMS appeared to indicate little or no conversion (based on the mass of the peak). The filtrate was subjected to 10% Pd/C hydrogenation on an H-Cube® reactor at 40° C. and 40 bar for 23 hours (the actual reaction time was less because of an error on the H-cube which stopped the reaction sometime during the night). LCMS appeared to show mostly desired product along with some starting material and a smallish byproduct. It was concentrated in vacuo, and the residue was dry loaded onto silica gel (1 g) and purified by flash chromatography (Analogix, 40 g SiO2, DCM to 95/5/0.5 DCM/MeOH/NH4OH gradient over 42 minutes) to give 1,1-dimethylethyl 4-{4-amino-3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-7-yl}-1-piperidinecarboxylate (91 mg) as an off-white solid.

Workup

  1. additionwas added
  2. filtrationfiltered
  3. customwas subjected to 10% Pd/C hydrogenation on an H-Cube® reactor at 40° C.
  4. wait40 bar for 23 hours (the actual reaction time was less because of an error on the H-cube which
  5. customthe reaction sometime during the night)

Sources & evidence

ORD record
ord-f62f422e22944f73b71187b946d7b90e
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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