Diisopropylethylamine → HCID 59239551, compound

HRID 1697964Notes

Reaction equation

HRID 1697964 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].C(N(CC)C(C)C)(C)C.Br[CH2:40][CH2:41][O:42][Si](C(C)(C)C)(C)C>C(#N)C.CN1CCCC1=O>[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]([CH2:40][CH2:41][OH:42])[CH2:19][C:17]=3[N:18]=2)=[CH:11][CH:12]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 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 59239551HCID 59239551, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a suspension of (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (301 mg, 0.759 mmol) in Acetonitrile (1.3 mL), N-Methylpyrrolidinone (0.44 mL) and N,N-Diisopropylethylamine (0.40 mL, 2.3 mmol) was added (2-Bromoethoxy)-tert-butyldimethylsilane (0.82 mL, 3.8 mmol), and the reaction was kept at 50° C. overnight. LC-MS showed the reaction was completed (desired peak m/z=555 (M+H)). The yellow solution was evaporated to dryness as much as possible, followed by dilution in Methylene chloride (6.0 mL) and Methanol (3.0 mL). Then, 4.0 M of Hydrogen chloride in 1,4-Dioxane (5.7 mL) was added, and the yellow solution was stirred at room temperature for 2.5 h. The solvents were removed and the residue was purified to give the final product ry (174.4 mg, 52% yield after two steps) as off-white powder: 1H NMR (400 MHz, DMSO) δ 8.65 (s, 1H), 8.15 (d, J=8.8 Hz, 2H), 7.47 (d, J=8.7 Hz, 2H), 6.18 (t, J=5.5 Hz, 1H), 4.48 (m, 1H), 4.12 (m, 1H), 3.87 (d, J=10.6 Hz, 1H), 3.75-3.48 (m, 8H), 3.40 (t, J=11.3 Hz, 1H), 3.17-3.04 (m, 2H), 2.80-2.53 (m, 6H), 1.22 (d, J=6.6 Hz, 3H), 1.06 (t, J=7.2 Hz, 3H); LC-MS m/z=441 (M+H).

Workup

  1. customThe yellow solution was evaporated to dryness as much as possible,
  2. additionThen, 4.0 M of Hydrogen chloride in 1,4-Dioxane (5.7 mL) was added
  3. customThe solvents were removed
  4. customthe residue was purified

Sources & evidence

ORD record
ord-e903208738574c8aa7d89419db70d50d
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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