Aniline → HCID 136331862, compound

HRID 1046982Notes

Reaction equation

HRID 1046982 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:23]4[C:24]5[CH:36]=[CH:35][CH:34]=[N:33][C:25]=5[NH:26][C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=5[C:22]4=[N:21][C:20]=3[CH2:37][C:38]([OH:40])=O)=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C(N=C=NCCCN(C)C)C.C(N(C(C)C)CC)(C)C>ClCCl>[O:40]=[C:38]([NH:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[CH2:37][C:20]1[N:21]=[C:22]2[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[NH:26][C:25]3[N:33]=[CH:34][CH:35]=[CH:36][C:24]=3[N:23]2[C:19]=1[C:16]1[CH:15]=[CH:14][C:13]([C:9]2([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH2:10][CH2:11][CH2:12]2)=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 6115AnilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 136390286HCID 136390286, compound

Product 1

HCID 136331862HCID 136331862, compoundYield 48.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-(3-(4-(1-((tert-butoxycarbonyl)amino)cyclobutyl)phenyl)-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-2-yl)acetic acid (0.04 g, 1 eq.) in dichloromethane (2 mL) was added successively aniline (0.027 g, 4 eq.), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) (0.029 g, 2 eq.) and diisopropylethylamine (70 μL, 5 eq.). The reaction was stirred at room temperature for 20 hours. The reaction mixture was diluted with dichloromethane (10 mL), washed with water (2×10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by preparative HPLC (YMC PACK ODS-AM; AM12S05-1020WT; 100×20 mm ID; CAN/0.1% TFA, 30 mL/min) gave tert-butyl (1-(4-(2-(2-oxo-2-(phenylamino)ethyl)-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-3-yl)phenyl)cyclobutyl)carbamate (0.022 g, 48%). LCMS: 613 [M+H].

Workup

  1. washwashed with water (2×10 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by preparative HPLC (YMC PACK ODS-AM; AM12S05-1020WT; 100×20 mm ID; CAN/0.1% TFA, 30 mL/min)

Sources & evidence

ORD record
ord-c3d11e3e57f14b7aad253403fb7681b4
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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