Triethylamine → Cyclopentyl-{4-[4-(6-fluoro-pyrido[3,4-d]pyrimidin-4-ylamino)-2-methyl-phenoxy]-piperidin-1-yl}-methanone

HRID 731905Notes

Reaction equation

HRID 731905 reaction equation
[CH:1]1([C:6](Cl)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[F:9][C:10]1[N:34]=[CH:33][C:13]2[N:14]=[CH:15][N:16]=[C:17]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)=[C:21]([CH3:32])[CH:20]=3)[C:12]=2[CH:11]=1.CCN(CC)CC>C(Cl)Cl>[CH:1]1([C:6]([N:29]2[CH2:28][CH2:27][CH:26]([O:25][C:22]3[CH:23]=[CH:24][C:19]([NH:18][C:17]4[C:12]5[CH:11]=[C:10]([F:9])[N:34]=[CH:33][C:13]=5[N:14]=[CH:15][N:16]=4)=[CH:20][C:21]=3[CH3:32])[CH2:31][CH2:30]2)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 78284Cyclopentanecarbonyl chlorideHCID 69051976(6-Fluoro-pyrido[3,4-d]pyrimidin-4-yl)-[3-methyl-4-(piperidin-4-yloxy)-phenyl]-amine

Product 1

HCID 69051928Cyclopentyl-{4-[4-(6-fluoro-pyrido[3,4-d]pyrimidin-4-ylamino)-2-methyl-phenoxy]-piperidin-1-yl}-methanoneYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Cyclopentane carbonyl chloride (0.187 g, 1.41 mmol) was added to a solution of (6-Fluoro-pyrido[3,4-d]pyrimidin-4-yl)-[3-methyl-4-(piperidin-4-yloxy)-phenyl]-amine (T) (0.50 g, 1.28 mmol) and NEt3 (0.38 g, 3.84 mmol) in CH2Cl2 (15 mL After 1 h the reaction was quenched with water, the layers were separated and the organic layer was washed with 1N NaOH and water, dried over Na2SO4, and concentrated. Purification by flash column chromatography (CH2Cl2/MeOH, 97/3) afforded the title compound as a yellow solid (0.40 g, 70%). LRMS: 450.3 (MH+); 1H NMR (DMSO-d6, 400 MHz): δ 9.90 (s, 1H), δ 8.86 (s, 1H), δ 8.58 (s, 1H), δ 8.19 (s, 1H), δ 7.54-7.56 (m, 2H), δ 7.04 (d, J=9.56 Hz, 1H) δ 4.58-4.61 (m, 1H), δ 3.70-3.72 (m, 2H), δ 3.33-3.44 (m, 2H), δ 2.93-3.008 (m, 1H), δ 2.17 (s, 3H), δ 1.46-1.94 (m, 12H).

Workup

  1. customwas quenched with water
  2. customthe layers were separated
  3. washthe organic layer was washed with 1N NaOH and water
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customPurification by flash column chromatography (CH2Cl2/MeOH, 97/3)

Sources & evidence

ORD record
ord-260bdb28b711417dbf25184766b98c68
Source dataset
uspto-grants-2009_09
Patent number
US07585869B2

Reaction notes

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