Dichloromethane → HCID 178480708, compound

HRID 1921777Notes

Reaction equation

HRID 1921777 reaction equation
C(OC(=O)[N:7]([C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)=[CH:32][CH:31]=1)[C:8]1[C:9]2[N:10]([CH:27]=[CH:28][N:29]=2)[C:11]([Sn](CCCC)(CCCC)CCCC)=[CH:12][N:13]=1)(C)(C)C.C(OC([N:51]1[C:55]([C:56]([F:59])([F:58])[F:57])=[C:54](Br)[CH:53]=[N:52]1)=O)(C)(C)C.C(Cl)Cl>CN(C=O)C.C(O)(C(F)(F)F)=O.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>[NH3:7].[CH3:42][N:39]1[CH2:40][CH2:41][N:36]([C:33]2[CH:34]=[CH:35][C:30]([NH:7][C:8]3[C:9]4[N:10]([CH:27]=[CH:28][N:29]=4)[C:11]([C:54]4[C:55]([C:56]([F:59])([F:58])[F:57])=[N:51][NH:52][CH:53]=4)=[CH:12][N:13]=3)=[CH:31][CH:32]=2)[CH2:37][CH2:38]1

Participants

8

Reactant 3

HCID 6344DichloromethaneHCID 59023088HCID 59023088, compoundHCID 67117498HCID 67117498, compound

Product 2

HCID 222AmmoniaHCID 178480708HCID 178480708, compoundYield 4.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

In the same way as described for Compound 145, step 2 using [4-(4-methyl-piperazin-1-yl)-phenyl]-(5-tributylstannanyl-imidazo[1,2-a]pyrazin-8-yl)-carbamic acid tert-butyl ester (0.38 g, 0.78 mmol) in DMF (6 mL), 4-bromo-5-trifluoromethyl-pyrazole-1-carboxylic acid tert-butyl ester (0.49 g, 0.15 mmol) and Pd(PPh3)4 (0.09 g, 0.15 mmol). The crude mixture is stirred in (1:1) TFA:DCM (2 mL) at room temperature for 3 hours. Purification by silica gel column chromatography eluting with DCM followed by a mixture of 99:1 and 95:5 DCM:NH3 (7M in MeOH) affords the title compound (2.79 mg, 1%). LCMS: Rt 1.90 min (96%) m/z (ES+) 443 (M+H)+; 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.26 (3H, s), 2.49-2.54 (4H, m), 3.09-3.14 (4H, m), 6.96 (2H, d), 7.31 (1H, s), 7.63 (2H, d), 7.89 (2H, d), 8.37 (1H, s), 9.44 (1H, s).

Workup

  1. customPurification by silica gel column chromatography
  2. washeluting with DCM
  3. additionfollowed by a mixture of 99:1 and 95:5 DCM

Sources & evidence

ORD record
ord-3fc4743a241544d1807bee85ef39dc49
Source dataset
uspto-grants-2012_05
Patent number
US08173656B2

Reaction notes

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