1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (1aR,3aR,5S,7aR,15aS,Z)-5-(2-(4-ethynylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yloxy)-9-methyl-N-(1-methylcyclopropylsulfonyl)-3,8-dioxo-1a,2,3,3a,4,5,6,7,7a,8,9,10,11,12,13,15a-hexadecahydro-1H-benzo[c]cyclopropa[g][1,6]diazacyclotetradecine-1a-carboxamide

HRID 926013Notes

Reaction equation

HRID 926013 reaction equation
[C:1]([C:3]1[N:4]=[C:5]([C:8]2[CH:17]=[C:16]([O:18][C@H:19]3[CH2:43][CH2:42][C@H:22]4[C:23](=[O:41])[N:24]([CH3:40])[CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][C@@H:31]5[CH2:36][C@@:32]5([C:37]([OH:39])=O)[NH:33][C:34](=[O:35])[C@@H:21]4[CH2:20]3)[C:15]3[C:10](=[C:11]([CH3:46])[C:12]([O:44][CH3:45])=[CH:13][CH:14]=3)[N:9]=2)[S:6][CH:7]=1)#[CH:2].[CH3:47]CN=C=NCCCN(C)C.C[NH:59][S:60]([CH:63]1[CH2:65][CH2:64]1)(=[O:62])=[O:61].C1CCN2C(=NCCC2)CC1>C(Cl)Cl>[C:1]([C:3]1[N:4]=[C:5]([C:8]2[CH:17]=[C:16]([O:18][C@H:19]3[CH2:43][CH2:42][C@H:22]4[C:23](=[O:41])[N:24]([CH3:40])[CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][C@@H:31]5[CH2:36][C@@:32]5([C:37]([NH:59][S:60]([C:63]5([CH3:47])[CH2:65][CH2:64]5)(=[O:62])=[O:61])=[O:39])[NH:33][C:34](=[O:35])[C@@H:21]4[CH2:20]3)[C:15]3[C:10](=[C:11]([CH3:46])[C:12]([O:44][CH3:45])=[CH:13][CH:14]=3)[N:9]=2)[S:6][CH:7]=1)#[CH:2]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15334537N-methylcyclopropanesulfonamideHCID 88050653(1aR,3aR,5S,7aR,15aS,Z)-5-(2-(4-ethynylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yloxy)-9-methyl-3,8-dioxo-1a,2,3,3a,4,5,6,7,7a,8,9,10,11,12,13,15a-hexadecahydro-1H-benzo[c]cyclopropa[g][1,6]diazacyclotetradecine-1a-carboxylic acid

Product 1

HCID 88050651(1aR,3aR,5S,7aR,15aS,Z)-5-(2-(4-ethynylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yloxy)-9-methyl-N-(1-methylcyclopropylsulfonyl)-3,8-dioxo-1a,2,3,3a,4,5,6,7,7a,8,9,10,11,12,13,15a-hexadecahydro-1H-benzo[c]cyclopropa[g][1,6]diazacyclotetradecine-1a-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To compound 46 (0.00003 mmol) in DCM (2 mL) under nitrogen was added EDCI (0.000062 mmol). The reaction mixture was stirred at room temperature for 2 hrs. Methyl-cyclopropylsulfonamide (0.00012 mmol) and DBU (0.00012 mmol) were then added and the reaction was stirred at room temperature for 16 hrs. DCM was then added, the mixture was washed with water and brine. Solvent was evaporated and the crude material was purified by silica gel chromatography (DCM/MeOH) to yield compound 52 as a white solid. MS (ESI, EI+): m/z=760 (MH+).

Workup

  1. stirringthe reaction was stirred at room temperature for 16 hrs
  2. washthe mixture was washed with water and brine
  3. customSolvent was evaporated
  4. customthe crude material was purified by silica gel chromatography (DCM/MeOH)

Sources & evidence

ORD record
ord-8f675c904444446990bdbe4c3ca96d1e
Source dataset
uspto-grants-2016_03
Patent number
US09284307B2

Reaction notes

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