Tetrahydrofuran → HCID 57737238, compound

HRID 1157568Notes

Reaction equation

HRID 1157568 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][N:31]([CH3:33])[CH3:32])[CH:25]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C1COCC1.C1C=CC2N(O)N=NC=2C=1.C[C:50]1[S:54][C:53]([C:55]2C=CC=CC=2)=N[C:51]=1[CH2:61][C:62]([OH:64])=O>CC(N(C)C)=O>[CH3:32][N:31]([CH2:30][C:26]1[CH:25]=[C:24]([NH:23][C:19]2[N:18]=[C:17]([C:16]3[C:8]([C:4]4[CH:3]=[C:2]([NH:1][C:62](=[O:64])[CH2:61][C:51]5[CH:55]=[CH:53][S:54][CH:50]=5)[CH:7]=[CH:6][CH:5]=4)=[N:9][N:10]4[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=34)[CH:22]=[CH:21][N:20]=2)[CH:29]=[CH:28][CH:27]=1)[CH3:33]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 757711-HydroxybenzotriazoleHCID 2760017(5-Methyl-2-phenyl-1,3-thiazol-4-yl)acetic acidHCID 57737209HCID 57737209, compound

Product 1

HCID 57737238HCID 57737238, compoundYield 77.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of 4-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-{3-[(dimethylamino)methyl]phenyl}-2-pyrimidinamine (50 mg, 0.115 mmol) (see Example 24, Step A) in 5:1 THF:DMA (2 mL) was added HOBT (46 mg, 0.34 mmol), 0.28 g polystyrene-bound carbodiimide resin (280 mg, 0.34 mmol), and (5-methyl-2-phenyl-1,3-thiazol-4-yl)acetic acid (80 mg, 0.34 mmol). After stirring at rt for 48 h, excess Dowex 550A OH anion-exchange resin was added and the resulting mixture was allowed to stir overnight. The solids were then removed by vacuum filtration and rinsed with THF (25 mL) and MeOH (25 mL). The filtrate was concentrated under reduced pressure and purified by column chromatography (DCM: 0-100% 90:9:1 DCM:MeOH:NH4OH(aq)) to afford the title compound (50.1 mg, 67%). 1H NMR (400 MHz, DMSO-d6) δ 2.11 (s, 6H), 2.43 (s, 3H), 3.31 (s, 2H), 3.81 (s, 2H), 6.45 (d, 1H, J=5.31 Hz), 6.84 (d, 1H, J=6.96 Hz), 7.08-7.11 (m, 1H), 7.14-7.18 (m, 1H), 7.23-7.25 (m, 1H), 7.38-7.46 (m, 5H), 7.59-7.62 (m, 1H), 7.68 (s, 1H), 7.75-7.81 (m, 3H), 7.89 (s, 1H), 8.21 (d, 1H, J=5.49 Hz), 8.48-8.51 (m, 1H), 8.79 (d, 1H, J=6.96 Hz) 9.50 (s, 1H), 10.35 (s, 1H). ES-LC/MS m/z=651 [M+H]+.

Workup

  1. stirringto stir overnight
  2. customThe solids were then removed by vacuum filtration
  3. washrinsed with THF (25 mL) and MeOH (25 mL)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. custompurified by column chromatography (DCM: 0-100% 90:9:1 DCM:MeOH:NH4OH(aq))

Sources & evidence

ORD record
ord-f0b57508aea4494eb4e070590ed8ad3a
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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