Dimethylformamide → HCID 59239156, compound

HRID 1698039Notes

Reaction equation

HRID 1698039 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].CN(C)C=O.[O:35]1[CH2:40][CH2:39][CH:38]([CH:41]=O)[CH2:37][CH2:36]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[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]([CH2:41][CH:38]4[CH2:39][CH2:40][O:35][CH2:36][CH2:37]4)[CH2:19][C:17]=3[N:18]=2)=[CH:11][CH:12]=1)=[O:5])[CH3:2]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 5049666Sodium triacetoxyborohydrideHCID 9964078Tetrahydro-2H-pyran-4-carboxaldehydeHCID 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 59239156HCID 59239156, compound

Conditions

Temperature
50 °C

Procedure

(S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (0.100 g, 0.252 mmol) in dry N,N-Dimethylformamide (1.00 mL, 12.9 mmol) at 0° C. was added tetrahydro-2H-pyran-4-carbaldehyde (0.02752 mL, 0.2522 mmol). The reaction mixture was stirred at 50° C. for 15 minutes then cooled at 0° C. and added Sodium triacetoxyborohydride (0.1069 g, 0.5044 mmol). The reaction mixture was allowed to warm slowly to room temperature and stirred for 2 hours. LC-MS shows mostly product. The reaction mixture was concentrated, chromatographed through silica gel (40 g, 0-5% MeOH in dichloromethane), and purified by HPLC. 1H NMR (400 MHz, DMSO) δ 8.62 (s, 1H), 8.15 (d, J=8.7, 2H), 7.46 (d, J=8.7, 2H), 6.16 (t, J=5.5, 1H), 4.13 (d, J=6.7, 1H), 3.85 (t, J=9.0, 3H), 3.70 (d, J=9.0, 1H), 3.61 (dd, J=12.3, 4.0, 4H), 3.52-3.31 (m, 4H), 3.17-3.07 (m, 2H), 2.67 (s, 3H), 2.51 (m, 1H), 2.34 (d, J=7.3, 2H), 1.90 (d, J=7.3, 1H), 1.66 (d, J=12.6, 2H), 1.28-1.10 (m, 5H), 1.06 (t, J=7.2, 3H). LC/MS-m/z+495.3 (M+H)+.

Workup

  1. temperaturethen cooled at 0° C.
  2. temperatureto warm slowly to room temperature
  3. stirringstirred for 2 hours
  4. concentrationThe reaction mixture was concentrated
  5. customchromatographed through silica gel (40 g, 0-5% MeOH in dichloromethane)
  6. custompurified by HPLC

Sources & evidence

ORD record
ord-588860b45ddd4670b041c11d82869486
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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