Diisopropylethylamine → 9-(6-((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridazinyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

HRID 79230Notes

Reaction equation

HRID 79230 reaction equation
[O:1]1[C:6]2([CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[CH2:5][NH:4][C:3](=[O:12])[CH2:2]1.[CH:13]1([N:18]2[C:22]3[N:23]=[C:24]([NH:27][C:28]4[N:33]=[N:32][C:31](Cl)=[CH:30][CH:29]=4)[N:25]=[CH:26][C:21]=3[C:20]3[CH:35]=[CH:36][N:37]=[CH:38][C:19]2=3)[CH2:17][CH2:16][CH2:15][CH2:14]1.C(N(CC)C(C)C)(C)C>CN1CCCC1=O>[CH:13]1([N:18]2[C:22]3[N:23]=[C:24]([NH:27][C:28]4[N:33]=[N:32][C:31]([N:9]5[CH2:8][CH2:7][C:6]6([O:1][CH2:2][C:3](=[O:12])[NH:4][CH2:5]6)[CH2:11][CH2:10]5)=[CH:30][CH:29]=4)[N:25]=[CH:26][C:21]=3[C:20]3[CH:35]=[CH:36][N:37]=[CH:38][C:19]2=3)[CH2:14][CH2:15][CH2:16][CH2:17]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 130594341-Oxa-4,9-diazaspiro(5.5)undecan-3-oneHCID 582996836-((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-chloro-pyridazine

Product 1

HCID 582997319-(6-((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridazinyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-oneYield 5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

To a mixture of compound 400 (110.0 mg, 646 μmol) and compound 140 (40.0 mg, 109 μmol) in N-methylpyrrolidinone (1.50 mL) was added N,N-diisopropylethylamine (DIEA) (0.100 mL, 575 μmol). The resulting mixture was heated at 160° C. under microwave irradiation for 6 h. The crude material was purified by reverse phase HPLC (acetonitrile/H2O containing 0.1% TFA each, 25 min from 10 to 40%). The isolated material was further purified by prep-TLC (10% methanol in DCM with 1% NH4OH) to give compound 396 as a yellow solid (2.5 mg, 5%). 1H NMR (500 MHz, CD3OD) δ 9.21 (s, 1 H) 8.91 (s, 1 H) 8.37-8.46 (m, 2 H) 8.08 (d, J=5.38 Hz, 1 H) 7.46 (d, J=10.03 Hz, 1 H) 5.43 (quin, 1 H) 4.21 (s, 2 H) 4.06 (ddd, J=13.27, 3.48, 3.30 Hz, 2 H) 3.37-3.42 (m, 4 H) 2.44 (dd, J=12.96, 8.31 Hz, 2 H) 2.08-2.24 (m, 4 H) 2.03 (d, J=13.45 Hz, 2 H) 1.84-1.93 (m, 2 H) 1.74-1.83 (m, 2 H) ppm; LCMS-ESI (POS), M/Z, M+1: Found 500.2, Calculated 500.2.

Workup

  1. customThe crude material was purified by reverse phase HPLC (acetonitrile/H2O containing 0.1% TFA each, 25 min from 10 to 40%)
  2. customThe isolated material was further purified by prep-TLC (10% methanol in DCM with 1% NH4OH)

Sources & evidence

ORD record
ord-2444c829e72b49b3866f59704b8086ff
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Reaction notes

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