Diisopropylethylamine → (+/-)-1-(2-(2,6-Dimethylphenyl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-2-methylpiperidin-4-ol

HRID 80769Notes

Reaction equation

HRID 80769 reaction equation
Cl[C:2]1[C:3]2[CH2:19][N:18]([C:20]3[N:24]([CH3:25])[N:23]=[C:22]([CH:26]([CH3:28])[CH3:27])[CH:21]=3)[CH2:17][CH2:16][C:4]=2[N:5]=[C:6]([C:8]2[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=2[CH3:15])[N:7]=1.C(N(C(C)C)CC)(C)C.Cl.[CH3:39][C@H:40]1[CH2:45][C@@H:44]([OH:46])[CH2:43][CH2:42][NH:41]1>CN(C)C(=O)C>[CH3:15][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]([CH3:14])[C:8]=1[C:6]1[N:7]=[C:2]([N:41]2[CH2:42][CH2:43][CH:44]([OH:46])[CH2:45][CH:40]2[CH3:39])[C:3]2[CH2:19][N:18]([C:20]3[N:24]([CH3:25])[N:23]=[C:22]([CH:26]([CH3:28])[CH3:27])[CH:21]=3)[CH2:17][CH2:16][C:4]=2[N:5]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 72207698(2S,4S)-2-Methylpiperidin-4-ol hydrochlorideHCID 86690253HCID 86690253, compound

Product 1

HCID 71240425(+/-)-1-(2-(2,6-Dimethylphenyl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-2-methylpiperidin-4-ol

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
125 °C

Procedure

To a solution of 4-chloro-2-(2,6-dimethylphenyl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (40 mg, 0.101 mmol) in N,N-dimethylacetamide (1.5 mL), was added diisopropylethylamine (0.141 mL, 0.808 mmol) and cis racemic-2-methylpiperidin-4-ol hydrochloride, (CAS#344329-35-7, 30.6 mg, 0.202 mmol). The reaction was heated to 125° C. for 42 h. After cooling, the mixture was directly purified via HPLC ((0.1% ammonium hydroxide in acetonitrile/water 35%-100%) to give 26 mg of product. 1H NMR (400 MHz, CD2Cl2) δ ppm 7.14-7.24 (m, 1 H), 7.04-7.12 (m, 2 H), 5.70 (s, 1 H), 4.15 (d, J=15.2 Hz, 1 H), 3.94 (d, J=15.4 Hz, 1 H), 3.78-3.91 (m, 1 H), 3.69 (s, 3H), 3.57-3.67 (m, 1 H), 3.27-3.39 (m, 2 H), 3.19-3.27 (m, 1 H), 3.02-3.12 (m, 2 H), 2.96 (ddd, J=12.8, 9.3, 3.2 Hz, 1 H), 2.86 (ddd, J=13.8, 7.1, 6.9 Hz, 1 H), 2.09 (s, 6 H), 1.87-2.02 (m, 2 H), 1.82 (d, J=3.0 Hz, 1 H), 1.56-1.71 (m, 1 H), 1.49 (dt, J=12.9, 8.3 Hz, 1 H), 1.22 (d, J=7.1 Hz, 6 H), 1.14 (d, J=6.3 Hz, 3 H); MS (ESI+) m/z 475.4 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. customthe mixture was directly purified via HPLC ((0.1% ammonium hydroxide in acetonitrile/water 35%-100%)

Sources & evidence

ORD record
ord-b9ea0c5ba6094f8d95bb279ca81550e1
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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