Hydrochloric Acid → HCID 59239111, compound

HRID 1698043Notes

Reaction equation

HRID 1698043 reaction equation
[C:1]([CH2:3][C@H:4]1[C:9]2[N:10]=[C:11]([C:21]3[CH:26]=[CH:25][C:24]([NH:27][C:28]([NH:30][CH2:31][CH3:32])=[O:29])=[CH:23][CH:22]=3)[N:12]=[C:13]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]3[CH3:20])[C:8]=2[CH2:7][CH2:6][N:5]1[CH2:33][CH3:34])#[N:2].C(N1CCC2C(N3CCOCC3)=NC(C3C=CC(NC(NCC)=O)=CC=3)=NC=2C1CC#N)(=O)C.Cl.[OH-].[Na+].CC1C=CC(COC(NNC(C2C=NC=CN=2)=O)=O)=CC=1>O1CCCC1>[C:1]([CH2:3][C@@H:4]1[C:9]2[N:10]=[C:11]([C:21]3[CH:26]=[CH:25][C:24]([NH:27][C:28]([NH:30][CH2:31][CH3:32])=[O:29])=[CH:23][CH:22]=3)[N:12]=[C:13]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]3[CH3:20])[C:8]=2[CH2:7][CH2:6][N:5]1[CH2:33][CH3:34])#[N:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 478568p-tolylmethyl N-(pyrazine-2-carbonylamino)carbamateHCID 59239462HCID 59239462, compoundHCID 67176423HCID 67176423, compound

Product 1

HCID 59239111HCID 59239111, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

and 1-(4-((S)-8-(cyanomethyl)-7-ethyl-4-((S)-3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea (xs2): 1-(4-(7-acetyl-8-(cyanomethyl)-4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea (0.051 g, 0.00011 mol) in dry Tetrahydrofuran (1.00 mL, 0.0123 mol) at 0° C. was added 1.0 M of Borane-THF complex in Tetrahydrofuran (0.320 mL) dropwise. The reaction mixture was allowed to warm slowly to room temperature and stirred overnight. 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, purified by HPLC, and the diastereomers were separated by SFC. R Diastereomer (xs1): 1H NMR (400 MHz, DMSO) δ 8.64 (s, 1H), 8.19 (t, J=11.3, 2H), 7.48 (d, J=8.7, 2H), 6.15 (t, J=5.3, 1H), 4.19 (d, J=6.6, 1H), 3.90 (d, J=11.6, 1H), 3.75 (d, J=12.2, 2H), 3.60 (dd, J=25.9, 11.5, 3H), 3.51-3.38 (m, 1H), 3.23-3.17 (m, 1H), 3.10 (ddd, J=24.6, 15.3, 9.3, 3H), 2.86 (dt, J=14.5, 7.2, 1H), 2.67 (s, 1H), 2.59 (dd, J=13.2, 6.9, 2H), 2.55-2.39 (m, 2H), 1.18 (d, J=6.6, 3H), 1.08 (dt, J=14.3, 7.1, 6H). LC/MS-m/z+464.2 (M+H)+; S Diastereomer (xs2) 1H NMR (400 MHz, DMSO) δ 8.63 (s, 1H), 8.20 (d, J=8.7, 2H), 7.48 (d, J=8.7, 2H), 6.15 (t, J=5.5, 1H), 4.14 (d, J=6.8, 1H), 3.88 (d, J=10.3, 1H), 3.81-3.70 (m, 2H), 3.70-3.57 (m, 3H), 3.39 (t, J=11.0, 1H), 3.14 (ddd, J=19.9, 12.1, 6.1, 4H), 3.07-2.98 (m, 1H), 2.84 (dq, J=13.9, 7.0, 1H), 2.59 (ddd, J=21.5, 15.3, 8.2, 4H), 1.34 (d, J=6.6, 3H), 1.08 (dt, J=14.3, 7.1, 6H). LC/MS-m/z+464.2 (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. custompurified by HPLC
  7. customthe diastereomers were separated by SFC

Sources & evidence

ORD record
ord-e8961546118b45ef96e0d92a928ac5e5
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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