Diisopropylethylamine → N-[2-Methoxy-4-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine

HRID 1842795Notes

Reaction equation

HRID 1842795 reaction equation
F[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([NH:11][C:12]2[N:17]=[C:16]([C:18]3[CH:19]=[N:20][N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][C:22]=34)[CH:15]=[CH:14][N:13]=2)=[C:4]([O:27][CH3:28])[CH:3]=1.Cl.Cl.[CH3:31][N:32]1[CH2:39][CH2:38][CH2:37][C:33]21[CH2:36][NH:35][CH2:34]2.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[CH3:28][O:27][C:4]1[CH:3]=[C:2]([N:35]2[CH2:36][C:33]3([N:32]([CH3:31])[CH2:39][CH2:38][CH2:37]3)[CH2:34]2)[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]=1[NH:11][C:12]1[N:17]=[C:16]([C:18]2[CH:19]=[N:20][N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][C:22]=23)[CH:15]=[CH:14][N:13]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 71240760N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine2×HCID 717431205-Methyl-2,5-diazaspiro[3.4]octane dihydrochloride2×

Product 1

HCID 71240861N-[2-Methoxy-4-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amineYield 84%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

N-(4-Fluoro-2-methoxy-5-nitrophenyl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (Intermediate 127, 300 mg, 0.78 mmol), 8-methyl-2,8-diazaspiro[3.4]octane (Intermediate 47, 118 mg, 0.94 mmol) and DIPEA (0.162 mL, 0.94 mmol) were heated at 100° C. in DMA (4 mL) for 1.75 h. The mixture was then absorbed onto an SCX column, then the column was washed with CH3OH and then eluted with 1:1 7M methanolic ammonia in CH2Cl2. Fractions that contained the desired product were combined and concentrated in vacuo. Purification by FCC, eluting with 2.5% 7N methanolic ammonia in CH2Cl2 gave the title compound (321 mg, 84%) as an orange foam; 1H NMR: 1.62-1.74 (2H, m), 1.74-1.85 (2H, m), 1.91-2.00 (2H, m), 2.00-2.06 (2H, m), 2.38 (3H, s), 2.65 (2H, t), 3.03 (2H, t), 3.71 (2H, d), 3.95 (3H, s), 4.04-4.15 (4H, m), 6.27 (1H, s), 7.01 (1H, d), 8.01 (1H, s), 8.09 (1H, s), 8.33 (1H, d), 8.54 (1H, s); m/z: ES′ MH+ 491.6.

Workup

  1. customThe mixture was then absorbed onto an SCX column
  2. washthe column was washed with CH3OH
  3. washeluted with 1:1 7M methanolic ammonia in CH2Cl2
  4. concentrationconcentrated in vacuo
  5. customPurification by FCC
  6. washeluting with 2.5% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-51597211e09e4503b742d739028855dc
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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