Dichloromethane → HCID 178480708, compound

HRID 1366153Notes

Reaction equation

HRID 1366153 reaction equation
C[N:2]1CCN(C2C=CC(NC3C4N(C=CN=4)C(C4SC=C(C(N)=O)C=4)=CN=3)=CC=2)CC1.C(OC(=O)[N:38]([C:61]1[CH:66]=[CH:65][C:64]([N:67]2[CH2:72][CH2:71][N:70]([CH3:73])[CH2:69][CH2:68]2)=[CH:63][CH:62]=1)[C:39]1[C:40]2[N:41]([CH:58]=[CH:59][N:60]=2)[C:42]([Sn](CCCC)(CCCC)CCCC)=[CH:43][N:44]=1)(C)(C)C.C(OC([N:82]1[C:86]([C:87]([F:90])([F:89])[F:88])=[C:85](Br)[CH:84]=[N:83]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>[NH3:2].[CH3:73][N:70]1[CH2:71][CH2:72][N:67]([C:64]2[CH:65]=[CH:66][C:61]([NH:38][C:39]3[C:40]4[N:41]([CH:58]=[CH:59][N:60]=4)[C:42]([C:85]4[C:86]([C:87]([F:90])([F:89])[F:88])=[N:82][NH:83][CH:84]=4)=[CH:43][N:44]=3)=[CH:62][CH:63]=2)[CH2:68][CH2:69]1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 59022988HCID 59022988, compoundHCID 59023088HCID 59023088, compoundHCID 67117498HCID 67117498, compound

Product 2

HCID 222AmmoniaHCID 178480708HCID 178480708, compoundYield 1%

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 (6mL), 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-17cd690fbf594a909603bc31115fd2d7
Source dataset
uspto-grants-2011_02
Patent number
US07893058B2

Reaction notes

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