3-iodo-2-methyl-2H-indazole → HCID 59605492, compound

HRID 1945759Notes

Reaction equation

HRID 1945759 reaction equation
[CH3:1][C:2]([N:7]1[CH2:12][CH2:11][N:10]([CH2:13][C:14]2[S:22][C:21]3[C:20]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=[N:19][C:18]([Sn](CCCC)(CCCC)CCCC)=[N:17][C:16]=3[CH:15]=2)[CH2:9][CH2:8]1)([CH3:6])[C:3]([NH2:5])=[O:4].I[C:43]1[N:44]([CH3:52])[N:45]=[C:46]2[C:51]=1[CH:50]=[CH:49][CH:48]=[CH:47]2>O1CCOCC1.S1C=CC=C1C([O-])=O.[Cu+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][C:2]([N:7]1[CH2:8][CH2:9][N:10]([CH2:13][C:14]2[S:22][C:21]3[C:20]([N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)=[N:19][C:18]([C:43]4[N:44]([CH3:52])[N:45]=[C:46]5[C:51]=4[CH:50]=[CH:49][CH:48]=[CH:47]5)=[N:17][C:16]=3[CH:15]=2)[CH2:11][CH2:12]1)([CH3:6])[C:3]([NH2:5])=[O:4]

Participants

6

Reactant 2

HCID 116013183-iodo-2-methyl-2H-indazoleHCID 575067302-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide

Product 1

HCID 59605492HCID 59605492, compoundYield 29%

Reagents, catalysts & solvents 3

HCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a degassed mixture of 2-methyl-2-(4-((4-morpholino-2-(tributylstannyl)thieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamide (270 mg, 0.389 mmol), 3-iodo-2-methyl-2H-indazole (95 mg, 0.368 mmol), copper(I) thiophene-2-carboxylate (70 mg, 0.368 mmol) in dioxane (2.3 mL) was added Pd(PPh3)4 (21 mg, 0.018 mmol). The reaction mixture was reacted in the CEM microwave at 140° C. for 30 min. The reaction mixture was then loaded onto a Biotage Isolute SPE SCX-2 column. The column was washed with MeOH and the desired product was then eluted with 2 M NH3 in MeOH and further purified by RP-HPLC to give 176 (44 mg, 29%). LCMS: M+H+=535.2. 1H-NMR (400 MHz, DMSO-d6): δ 8.40 (d, 1H), 7.67 (d, 1H), 7.47 (s, 1H), 7.31 (t, 1H), 7.19 (t, 1H), 7.06 (s, 1H), 6.93 (s, 1H), 4.60 (s, 3H), 4.06 (m, 4H), 3.88 (s, 2H), 3.84 (m, 4H), 2.49-2.62 (m, 8H), 1.08 (s, 6H)

Workup

  1. customThe reaction mixture was reacted in the CEM microwave at 140° C. for 30 min
  2. washThe column was washed with MeOH
  3. washthe desired product was then eluted with 2 M NH3 in MeOH
  4. customfurther purified by RP-HPLC

Sources & evidence

ORD record
ord-ddb14f3bb0944a65aca1bd41b07abda6
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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