4-(Tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide → 4-[8-(4-Methanesulfonyl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-benzamide

HRID 1921746Notes

Reaction equation

HRID 1921746 reaction equation
N1(C2C=CC(NC3C4N(C=CN=4)C(C4C=CNC(=O)C=4)=CN=3)=CC=2)CCOCC1.CC1(C)C(C)(C)OB([C:38]2[CH:46]=[CH:45][C:41]([C:42]([NH2:44])=[O:43])=[CH:40][CH:39]=2)O1.Br[C:49]1[N:54]2[CH:55]=[CH:56][N:57]=[C:53]2[C:52]([NH:58][C:59]2[CH:64]=[CH:63][C:62]([S:65]([CH3:68])(=[O:67])=[O:66])=[CH:61][CH:60]=2)=[N:51][CH:50]=1.CC([O-])(C)C.[Na+]>CN(C=O)C.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>[CH3:68][S:65]([C:62]1[CH:63]=[CH:64][C:59]([NH:58][C:52]2[C:53]3[N:54]([CH:55]=[CH:56][N:57]=3)[C:49]([C:38]3[CH:39]=[CH:40][C:41]([C:42]([NH2:44])=[O:43])=[CH:45][CH:46]=3)=[CH:50][N:51]=2)=[CH:60][CH:61]=1)(=[O:66])=[O:67]

Participants

8

Reactant 4

HCID 27605884-(Tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 23676156Sodium t-butoxideHCID 248574474-[8-(4-Morpholin-4-yl-phenylamino)imidazo[1,2-a]pyrazin-5-yl]-1H-pyridin-2-oneHCID 59022984(5-Bromo-imidazo[1,2-a]pyrazin-8-yl)-(4-methanesulfonyl-phenyl)-amine

Product 1

HCID 248576534-[8-(4-Methanesulfonyl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-benzamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In the same way as described for Compound 85, step 1, using 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (1.0 g, 6.11 mmol), (5-bromo-imidazo[1,2-a]pyrazin-8-yl)-(4-methanesulfonyl-phenyl)-amine (1.49 g, 4.07 mmol), Pd(PPh3)4 (471 mg, 0.41 mmol) and NaOtBu (1.57 g, 0.82 mmol) in DMF (18 mL) and water (6 mL). The residue is chromatographed on silica gel, eluting with DCM followed by 95:5 DCM:NH3 (7M in MeOH), and the fractions containing the desired product are combined and evaporated to afford a solid, crystallised in ethyl acetate (566 mg, 34%). LCMS: Rt 2.53 min (99%), m/z (APCI) 408 (M+H)+; 1H-NMR (400 MHz, d6-DMSO δ(ppm) 3.21 (3H, s), 7.54 (1H, br s), 7.67 (1H, s), 7.81 (1H, s), 7.86-7.92 (4H, m), 8.09-8.17 (3H, m), 8.21 (1H, br s), 8.41 (2H, d), 10.32 (1H, s).

Workup

  1. customThe residue is chromatographed on silica gel
  2. washeluting with DCM
  3. additionNH3 (7M in MeOH), and the fractions containing the desired product
  4. customevaporated
  5. customto afford a solid
  6. customcrystallised in ethyl acetate (566 mg, 34%)

Sources & evidence

ORD record
ord-c7cecd6c58ef40669f9ce12aad222359
Source dataset
uspto-grants-2012_05
Patent number
US08173656B2

Reaction notes

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