Diisopropylethylamine → (S)-6-(3-Isopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3-methyl-1H-indol-4-yl)-4-(2-methylpiperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80815Notes

Reaction equation

HRID 80815 reaction equation
Cl[C:2]1[C:3]2[CH2:21][N:20]([C:22]3[N:26]([CH3:27])[N:25]=[C:24]([CH:28]([CH3:30])[CH3:29])[CH:23]=3)[CH2:19][CH2:18][C:4]=2[N:5]=[C:6]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[C:10]([CH3:17])=[CH:11][NH:12]3)[N:7]=1.C(N(C(C)C)CC)(C)C.[CH3:40][C@H:41]1[CH2:46][CH2:45][CH2:44][CH2:43][NH:42]1>CN(C)C(=O)C>[CH:28]([C:24]1[CH:23]=[C:22]([N:20]2[CH2:19][CH2:18][C:2]3[N:7]=[C:6]([C:8]4[CH:16]=[CH:15][CH:14]=[C:13]5[C:9]=4[C:10]([CH3:17])=[CH:11][NH:12]5)[N:5]=[C:4]([N:42]4[CH2:43][CH2:44][CH2:45][CH2:46][C@@H:41]4[CH3:40])[C:3]=3[CH2:21]2)[N:26]([CH3:27])[N:25]=1)([CH3:29])[CH3:30]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 6427443(S)-(+)-2-MethylpiperidineHCID 866902644-chloro-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Product 1

HCID 71244844(S)-6-(3-Isopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3-methyl-1H-indol-4-yl)-4-(2-methylpiperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
125 °C

Procedure

To a solution of 4-chloro-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (50 mg, 0.123 mmol) in N,N-dimethylacetamide (1.5 mL), was added diisopropylethylamine (0.15 mL, 0.86 mmol) and (S)-2-methylpiperidine (37 mg, 0.37 mmol). The reaction was stirred and heated to 125° C. for 24 h. After cooling, the mixture was directly purified via HPLC ((0.1% ammonium hydroxide in acetonitrile)/water=35%-100%). 1H NMR (400 MHz, CD2Cl2) δ ppm 8.23 (br. s., 1 H), 7.42 (d, J=8.1 Hz, 1 H), 7.33 (d, J=8.1 Hz, 1 H), 7.16-7.26 (m, 1 H), 7.04 (s, 1 H), 5.69 (s, 1 H), 4.06-4.16 (m, 1 H), 3.90-4.06 (m, 2 H), 3.67 (s, 3 H), 3.53 (d, J=13.4 Hz, 1 H), 3.29-3.40 (m, 2 H), 3.16-3.29 (m, 1 H), 3.10 (d, J=4.5 Hz, 2 H), 2.85 (dt, J=13.8, 6.9 Hz, 1 H), 2.10 (s, 3 H), 1.74-1.91 (m, 2 H), 1.65-1.74 (m, 2 H), 1.48-1.65 (m, 2 H), 1.22 (d, J=6.8 Hz, 6 H); MS (ESI+) m/z 484.4 (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-6fb42ff917524f1980cfe70188d37080
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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