1,2-Dichloroethane → GDC-0349

HRID 1697938Notes

Reaction equation

HRID 1697938 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:23]3[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]3[CH3:29])[C:16]3[CH2:22][CH2:21][NH:20][CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2].[O:30]1[CH2:33][C:32](=O)[CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].ClCCCl>C([O-])(O)=O.[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:23]3[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]3[CH3:29])[C:16]3[CH2:22][CH2:21][N:20]([CH:32]4[CH2:33][O:30][CH2:31]4)[CH2:19][C:17]=3[N:18]=2)=[CH:11][CH:12]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 150242543-OxetanoneHCID 46913570Urea, N-ethyl-N'-[4-[5,6,7,8-tetrahydro-4-[(3S)-3-Methyl-4-Morpholinyl]pyrido[3,4-d]pyriMidin-2-yl]phenyl]-

Product 1

HCID 59239165GDC-0349

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (ca) (1.0 g, 2.5 mmol), 3-oxetanone (0.91 mL, 13 mmol) and sodium triacetoxyborohydride (1.7 g, 8.1 mmol) in 1,2-dichloroethane (25 mL, 320 mmol) was stirred at 70° C. under N2 for 3 h. The mixture was then cooled down and poured in diluted NaHCO3. The organic and aqueous phases were separated. The aqueous phase was extracted with 2×50 mL of DCM. The combined organic phases were dried with Magnesium sulfate, filtered and concentrated. The crude solid was purified by flash chromatography (100% DCM to 5% MeOH/DCM) to provide product ih as a pale yellow solid: 1H NMR (400 MHz, DMSO) δ 8.61 (s, 1H), 8.15 (d, J=8.7 Hz, 2H), 7.46 (d, J=8.7 Hz, 2H), 6.15 (s, 1H), 4.64 (t, J=6.5 Hz, 2H), 4.55 (d, J=5.9 Hz, 2H), 4.13 (d, J=6.7 Hz, 1H), 3.87 (d, J=11.4 Hz, 1H), 3.62 (dd, J=34.1, 22.2 Hz, 6H), 3.43 (d, J=16.1 Hz, 2H), 3.20-3.04 (m, 2H), 2.69 (d, J=4.6 Hz, 3H), 1.24 (d, J=6.6 Hz, 3H), 1.06 (t, J=7.2 Hz, 3H); LC-MS: m/z=+453 (M+H)+.

Workup

  1. temperatureThe mixture was then cooled down
  2. customThe organic and aqueous phases were separated
  3. extractionThe aqueous phase was extracted with 2×50 mL of DCM
  4. dry with materialThe combined organic phases were dried with Magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude solid was purified by flash chromatography (100% DCM to 5% MeOH/DCM)
  8. customto provide product ih as a pale yellow solid

Sources & evidence

ORD record
ord-9f458c2d1f264460b3c450fdf08c60b0
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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