Methyl iodide → HCID 67503395, compound

HRID 1047043Notes

Reaction equation

HRID 1047043 reaction equation
Cl[C:2]1[N:3]=[C:4]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[NH:8][C:7]3[N:15]=[CH:16][CH:17]=[CH:18][C:6]=3[N:5]2[C:19]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]2([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1.[OH:38][C:39]1[CH:48]=[C:47](B2OC(C)(C)C(C)(C)O2)[CH:46]=[CH:45][C:40]=1[C:41]([O:43][CH3:44])=[O:42].C([O-])([O-])=O.[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C.CCOC(C)=O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[C:33]([O:32][C:31]([NH:30][C:26]1([C:23]2[CH:24]=[CH:25][C:20]([C:19]3[N:5]4[C:6]5[CH:18]=[CH:17][CH:16]=[N:15][C:7]=5[NH:8][C:9]5[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=5[C:4]4=[N:3][C:2]=3[C:47]3[CH:46]=[CH:45][C:40]([C:41]([O:43][CH3:44])=[O:42])=[C:39]([OH:38])[CH:48]=3)=[CH:21][CH:22]=2)[CH2:29][CH2:28][CH2:27]1)=[O:37])([CH3:35])([CH3:34])[CH3:36]

Participants

9

Reactant 5

HCID 6328Methyl iodideHCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 17998928Methyl 2-hydroxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 136331866tert-butyl {1-[4-(2-chloro-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

Product 1

HCID 67503395HCID 67503395, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-butyl {1-[4-(2-chloro-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (55 mg, 0.092 mmol), methyl 2-hydroxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (48 mg, 0.18 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (7 mg, 0.009 mmol), and 2M Na2CO3 aq. (0.092 mL, 0.18 mmol) in DMF (2.5 mL) was treated with microwave (160° C. for 1 hour). The reaction mixture was added potassium carbonate (30 mg, 0.22 mmol) and iodomethane (0.050 mL, 0.80 mmol) and stirred at r.t for 8.5 hours. The mixture was diluted with AcOEt, washed with water(×3), brine, dried over Na2SO4, then filtrated through Celite pad. The filtrate was concentrated and the residue was purified by preparative thin-layer chromatography (n-hexane/AcOEt=1:2) to afford the desired product (33 mg, 57%) as a pale yellow solid. 1HNMR (CDCl3) 400 MHz δ: 8.16 (dd, J=8.0 Hz and 1.1 Hz, 1H), 8.01 (d, J=4.0 Hz, 1H), 7.70 (d, J=8.6 Hz, 1H), 7.39 (d, J=8.6 Hz, 2H), 7.31 (td, J=8.0 Hz and 1.1 Hz, 2H), 7.18-7.16 (m, 2H), 7.11-7.07 (m, 1H), 6.95 (d, J=8.0 Hz, 1H), 6.80-6.76 (m, 1H), 6.59 (dd, J=7.7 Hz and 4.9 Hz, 1H), 6.24 (s, 1H), 5.09 (br s, 1H), 3.92 (s, 3H), 2.59-2.40 (m, 4H), 2.19-2.12 (m, 1H), 1.93-1.88 (m, 1H), 1.40 (br s, 9H). LCMS: 630 [M+H].

Workup

  1. additionwas treated with microwave (160° C. for 1 hour)
  2. washwashed with water(×3), brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltrated through Celite pad
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by preparative thin-layer chromatography (n-hexane/AcOEt=1:2)

Sources & evidence

ORD record
ord-d03bef490f5449ce8dd445018c061978
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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