Hydrochloric Acid → HCID 59239354, compound

HRID 1698034Notes

Reaction equation

HRID 1698034 reaction equation
[C:1]([N:4]1[CH2:13][CH2:12][C:11]2[C:10]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]3[CH2:20][CH3:21])=[N:9][C:8]([C:22]3[CH:27]=[CH:26][C:25]([NH:28][C:29]([NH:31][CH2:32][CH3:33])=[O:30])=[CH:24][CH:23]=3)=[N:7][C:6]=2[CH2:5]1)(=O)[CH3:2].Cl.[OH-].[Na+].CC1C=CC(COC(NNC(C2C=NC=CN=2)=O)=O)=CC=1>O1CCCC1>[CH2:32]([NH:31][C:29]([NH:28][C:25]1[CH:24]=[CH:23][C:22]([C:8]2[N:9]=[C:10]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]3[CH2:20][CH3:21])[C:11]3[CH2:12][CH2:13][N:4]([CH2:1][CH3:2])[CH2:5][C:6]=3[N:7]=2)=[CH:27][CH:26]=1)=[O:30])[CH3:33]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 478568p-tolylmethyl N-(pyrazine-2-carbonylamino)carbamateHCID 59239122HCID 59239122, compound

Product 1

HCID 59239354HCID 59239354, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

(S)-1-(4-(7-acetyl-4-(3-ethylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea (0.106 g, 0.000234 mol) in dry Tetrahydrofuran (2.10 mL, 0.0259 mol) at 0° C. was added 1.0 M of Borane-THF complex in Tetrahydrofuran (0.92 mL) dropwise. The reaction mixture was warmed to room temperature and for 1 hour. The reaction mixture was cooled at 0° C. then about 1 mL 1M HCl dropwise then added 1M NaOH until pH10. The reaction mixture was extracted three times with 10% MeOH in dichloromethane, dried over Magnesium sulfate, filtered, concentrated, was chromatographed through silica gel (12 g, 0-5% MeOH on dichloromethane), and submitted for purification. 1H NMR (400 MHz, DMSO) δ 8.61 (s, 1H), 8.15 (d, J=8.7, 2H), 7.46 (d, J=8.8, 2H), 6.15 (t, J=5.5, 1H), 3.97 (s, 1H), 3.85 (d, J=10.4, 1H), 3.78 (d, J=11.3, 1H), 3.74-3.62 (m, 3H), 3.55 (t, J=11.2, 1H), 3.40 (t, J=13.4, 2H), 3.18-3.05 (m, 2H), 2.85-2.69 (m, 2H), 2.63-2.47 (m, 3H), 2.43 (d, J=9.0, 1H), 1.76 (ddt, J=38.0, 13.8, 7.1, 2H), 1.11 (t, J=7.1, 3H), 1.06 (t, J=7.2, 3H), 0.82 (t, J=7.4, 3H). LC/MS-m/z+439.2 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled at 0° C.
  2. extractionThe reaction mixture was extracted three times with 10% MeOH in dichloromethane
  3. dry with materialdried over Magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customwas chromatographed through silica gel (12 g, 0-5% MeOH on dichloromethane)
  7. customsubmitted for purification

Sources & evidence

ORD record
ord-e057ae9b407748efaa4fa795ec72a0f4
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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