1,1'-Carbonyldiimidazole → HCID 68182919, compound

HRID 1618330Notes

Reaction equation

HRID 1618330 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([NH:11][C:12]3[N:17]=[C:16]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])[N:15]=[C:14]([NH:24][C:25]4[CH:48]=[CH:47][C:28]([C:29]([NH:31][CH2:32][CH2:33][CH2:34][C:35]([NH:37][C@:38]5([C:44]([OH:46])=O)[CH2:40][C@H:39]5[CH:41]5[CH2:43][CH2:42]5)=[O:36])=[O:30])=[CH:27][CH:26]=4)[N:13]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:61][S:62]([NH2:65])(=[O:64])=[O:63].C1CCN2C(=NCCC2)CC1>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([NH:11][C:12]3[N:17]=[C:16]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])[N:15]=[C:14]([NH:24][C:25]4[CH:48]=[CH:47][C:28]([C:29]([NH:31][CH2:32][CH2:33][CH2:34][C:35]([NH:37][C@:38]5([C:44](=[O:46])[NH:65][S:62]([CH3:61])(=[O:64])=[O:63])[CH2:40][C@H:39]5[CH:41]5[CH2:42][CH2:43]5)=[O:36])=[O:30])=[CH:27][CH:26]=4)[N:13]=3)[CH2:9][CH2:10]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 68183076HCID 68183076, compound

Product 1

HCID 68182919HCID 68182919, compoundYield 43.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of (1S,2R)-2-(4-(4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzamido)butanamido)bi(cyclopropane)-2-carboxylic acid (15 mg, 0.02 mmol) in THF solution was added CDI (7.0 mg, 0.04 mmol). The mixture was heated at 65° C. for 1 hour. After cooling to room temperature, methanesulfonamide (4.2 mg, 0.04 mmol) and DBU (9.9 ul, 0.07 mmol) were added to the mixture. The reaction mixture was stirred at r.t. for 16 hours. The solvent was evaporated and the residue was purified by preparative HPLC to afford 4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)-N-(4-((1S,2R)-2-(methylsulfonylcarbamoyl)bi(cyclopropan)-2-ylamino)-4-oxobutyl)benzamide (6.7 mg, 40%) as a white solid. 1H NMR (400 MHz, MeOD) δ ppm 0.34 (m, 2H), 0.57 (q, J=9.20 Hz, 2H), 0.71-0.80 (m, 1H), 1.08-1.13 (m, 1H), 1.18 (ddd, J=9.41, 7.53, 7.40 Hz, 1H), 1.34-1.45 (m, 4H), 1.77 (dd, J=7.53, 5.02 Hz, 1H), 1.85-1.97 (m, 1H), 2.26-2.36 (m, 2H), 2.37 (m, 2H), 3.26 (s, 3H), 3.41-3.51 (m, 1H), 4.00 (s, 2H), 7.23-7.33 (m, 4H), 7.60-7.75 (m, 3H), 7.85 (m, 1H); LC-MS (Condition A), MS m/z 765.1 (M++H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe solvent was evaporated
  3. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-5348171ae08c402a883cafbba9c0f89a
Source dataset
uspto-grants-2014_07
Patent number
US08765944B2

Reaction notes

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