Sodium Carbonate → HCID 69087722, compound

HRID 1047049Notes

Reaction equation

HRID 1047049 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.[CH2:38]([O:45][C:46]1[CH:51]=[CH:50][C:49](B(O)O)=[CH:48][CH:47]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.C([O-])([O-])=O.[Na+].[Na+]>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](=[O:37])[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:49]3[CH:50]=[CH:51][C:46]([O:45][CH2:38][C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[CH:47][CH:48]=3)=[CH:21][CH:22]=2)[CH2:27][CH2:28][CH2:29]1)([CH3:36])([CH3:35])[CH3:34]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343144-Benzyloxy-phenylboronic acidHCID 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 69087722HCID 69087722, compoundYield 84%

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 (400 mg, 0.778 mmol), [4-(benzyloxy)phenyl]boronic acid (355 mg, 1.56 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (55 mg, 0.078 mmol), and 2M Na2CO3 aq. (0.780 mL, 1.56 mmol) in DMF (8 mL) was treated with microwave (160° C. for 1 hour). 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 column chromatography (n-hexane/AcOEt=3:2) to afford the mixture of the desired product (430 mg, 84%) as a pale yellow solid. 1HNMR (CDCl3) 400 MHz δ: 8.16 (dd, J=8.0, 1.1 Hz, 1H), 8.00 (d, J=4.0 Hz, 1H), 7.51 (d, J=8.0 Hz, 2H), 7.43 (d, J=8.0 Hz, 2H), 7.39-7.33 (m, 4H), 7.32-7.28 (m, 2H), 7.16-7.12 (m, 3H), 6.94 (d, J=8.0 Hz, 1H), 6.89 (d, J=8.6 Hz, 2H), 6.79 (d, J=7.4 Hz, 1H), 6.59 (dd, J=8.0, 4.6 Hz, 1H), 6.26 (s, 1H), 5.10 (br s, 1H), 5.05 (s, 2H), 2.56-2.46 (m, 4H), 2.18-2.09 (m, 1H), 1.93-1.84 (m, 1H), 1.39 (br s, 9H). LCMS: 662 [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 column chromatography (n-hexane/AcOEt=3:2)
  7. customto afford

Sources & evidence

ORD record
ord-79cd3a1a1cfa480e882cd36cdc7049c6
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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