Acetic Acid → HCID 59239087, compound

HRID 1698023Notes

Reaction equation

HRID 1698023 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][C@@H:27]3[CH3:32])[C:16]3[CH2:22][CH2:21][N:20]([CH2:23][CH3:24])[C@@H:19]([CH3:25])[C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2].C(NC(NC1C=CC(C2N=C(N3CCOC[C@@H]3C)C3CCNC(C)C=3N=2)=CC=1)=O)C.CN(C)C=O.C(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>[OH-].[Na+]>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[N:14]=[C:15]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][C@@H:27]3[CH3:32])[C:16]3[CH2:22][CH2:21][N:20]([CH2:23][CH3:24])[C@H:19]([CH3:25])[C:17]=3[N:18]=2)=[CH:11][CH:12]=1)=[O:5])[CH3:2]

Participants

8

Reactant 6

HCID 176Acetic Acid2×HCID 177Acetaldehyde2×HCID 6228Dimethylformamide2×HCID 5049666Sodium triacetoxyborohydride2×HCID 59239642HCID 59239642, compoundHCID 67178079HCID 67178079, compound

Product 1

HCID 59239087HCID 59239087, compound

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent2×

Procedure

and 1-ethyl-3-(4-((S)-7-ethyl-8-methyl-4-((S)-3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (ws2): (1-Ethyl-3-(4-(8-methyl-4-((S)-3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (0.172 g, 0.419 mmol) in dry N,N-Dimethylformamide (2.00 mL, 25.8 mmol) at 0° C. was added Acetaldehyde (0.0236 mL, 0.420 mmol). The reaction mixture was stirred at 0° C. for 5 minutes the added Sodium triacetoxyborohydride (0.182 g, 0.859 mmol) followed by Acetic acid (0.0476 mL, 0.838 mmol). The reaction mixture was allowed to warm slowly to room temperature and stirred overnight. The reaction mixture was diluted with 1 M NaOH, extracted three times with 10% MeOH in dichloromethane, dried over Magnesium sulfate, filtered, and concentrated. The reaction mixture was redissovled in dry N,N-Dimethylformamide (2.00 mL, 25.8 mmol) cooled at 0° C., then added Acetaldehyde (0.0236 mL, 0.420 mmol). The reaction mixture was stirred at 0° C. for 5 minutes then added Sodium triacetoxyborohydride (0.181 g, 0.854 mmol) followed by Acetic acid (0.0476 mL, 0.837 mmol). The reaction mixture was stirred for 3 days. The reaction mixture was diluted with 1M NaOH, 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 (ws1): 1H NMR (400 MHz, DMSO) δ 8.66 (s, 1H), 8.17 (d, J=8.7, 2H), 7.47 (d, J=8.8, 2H), 6.19 (t, J=5.6, 1H), 4.12 (d, J=6.7, 1H), 3.87 (d, J=11.1, 1H), 3.73 (dd, J=11.3, 2.7, 1H), 3.64-3.49 (m, 4H), 3.47-3.38 (m, 2H), 3.16-3.09 (m, 2H), 3.01-2.93 (m, 1H), 2.80 (dq, J=14.5, 7.3, 1H), 2.67 (t, J=7.4, 1H), 2.60-2.53 (m, 1H), 2.41-2.31 (m, 1H), 1.42 (d, J=6.6, 3H), 1.18 (d, J=6.6, 3H), 1.14 (t, J=7.2, 3H), 1.06 (t, 3H). LC/MS-m/z+439.3 (M+H)+; and S-Diastereomer (ws2): 1H NMR (400 MHz, DMSO) δ 8.65 (s, 1H), 8.17 (d, J=8.7, 2H), 7.47 (d, J=8.8, 2H), 6.19 (t, J=5.5, 1H), 4.08 (d, J=6.7, 1H), 3.86 (d, J=11.3, 1H), 3.71-3.55 (m, 5H), 3.39 (d, J=11.4, 1H), 3.16-3.08 (m, 2H), 2.90 (dd, J=11.6, 4.7, 1H), 2.74 (dq, J=14.3, 7.2, 1H), 2.69-2.53 (m, 3H), 2.47-2.40 (m, 1H), 1.38 (d, J=6.6, 3H), 1.29 (d, J=6.6, 3H), 1.13 (t, J=7.2, 3H), 1.07 (t, 3H).

Workup

  1. extractionextracted three times with 10% MeOH in dichloromethane
  2. dry with materialdried over Magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. temperaturecooled at 0° C.
  6. stirringThe reaction mixture was stirred at 0° C. for 5 minutes
  7. stirringThe reaction mixture was stirred for 3 days
  8. extractionextracted three times with 10% MeOH in dichloromethane
  9. dry with materialdried over Magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified by HPLC
  13. customthe diastereomers were separated by SFC

Sources & evidence

ORD record
ord-50ca67edf05148efb87241b8a80cd5a8
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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