Water → Tert-butyl 13-cyclohexyl-3-methoxy-6-(4-(4-morpholinylcarbonyl)-1,3-oxazol-5-yl)-7h-indolo[2,1-a][2]benzazepine-10-carboxylate

HRID 1097796Notes

Reaction equation

HRID 1097796 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:9]=[CH:10][C:11]2[C:12]([CH:36]3[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)=[C:13]3[C:19]4[CH:20]=[CH:21][C:22]([O:24][CH3:25])=[CH:23][C:18]=4[CH:17]=[C:16]([C:26]4[O:30][CH:29]=[N:28][C:27]=4[C:31]([OH:33])=O)[CH2:15][N:14]3[C:34]=2[CH:35]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[NH:64]1[CH2:69][CH2:68][O:67][CH2:66][CH2:65]1.O>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH:36]1([C:12]2[C:11]3[CH:10]=[CH:9][C:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])=[CH:35][C:34]=3[N:14]3[CH2:15][C:16]([C:26]4[O:30][CH:29]=[N:28][C:27]=4[C:31]([N:64]4[CH2:69][CH2:68][O:67][CH2:66][CH2:65]4)=[O:33])=[CH:17][C:18]4[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:19]=4[C:13]=23)[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]1

Participants

7

Reactant 4

HCID 962WaterHCID 8083MorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 591337975-(10-(Tert-butoxycarbonyl)-13-cyclohexyl-3-methoxy-7h-indolo[2,1-a][2]benzazepin-6-yl)-1,3-oxazole-4-carboxylic acid

Product 1

HCID 59133924Tert-butyl 13-cyclohexyl-3-methoxy-6-(4-(4-morpholinylcarbonyl)-1,3-oxazol-5-yl)-7h-indolo[2,1-a][2]benzazepine-10-carboxylateYield 109%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

5-(10-(tert-Butoxycarbonyl)-13-cyclohexyl-3-methoxy-7H-indolo[2,1-a][2]benzazepin-6-yl)-1,3-oxazole-4-carboxylic acid (185 mg, 0.334 mmol) was dissolved in DMF (3.2 ml), and O-benzotriazol-1-yl-N,N,N′,N′-tetra-methyluronium tetrafluoroborate (193 mg, 0.600 mmol) was added. The reaction was stirred capped at room temperature for 25 minutes and DMAP (163 mg, 1.334 mmol) was dissolved in the reaction then morpholine (0.058 ml, 0.667 mmol) was added. The reaction was capped and stirred at room temperature overnight. The reaction was poured into 30 ml of water and extracted with dichloromethane. The organic layer was washed sequentially with 0.1M aqueous citric acid, 0.1M aqueous NaH2PO4, then dried over anhydrous sodium sulfate. The sample was filtered, volatiles removed and the sample dried in vacuo to obtain 227 mg of an amorphous orange solid. 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 1.16-1.50 (m, 7H) 1.53-1.61 (m, 6H) 1.62 (s, 10H) 1.76 (d, J=10.38 Hz, 2H) 1.83-2.15 (m, 5H) 3.40-3.84 (m, 7H) 3.83-3.95 (m, 5H) 4.40 (d, J=11.60 Hz, 1H) 5.64 (d, J=12.21 Hz, 1H) 6.97 (d, J=2.75 Hz, 1H) 7.05 (dd, J=8.39, 2.59 Hz, 1H) 7.50 (d, J=8.55 Hz, 1H) 7.53 (s, 1H) 7.65 (d, J=8.24 Hz, 1H) 7.77-7.86 (m, 2H) 7.97-8.04 (m, 1H) 8.10 (s, 1H). LC-MS retention time 2.64 min m/z 624 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Xterra MS 7u C18 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 2 min, and an analysis time of 5 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. customcapped at room temperature for 25 minutes
  2. customThe reaction was capped
  3. stirringstirred at room temperature overnight
  4. extractionextracted with dichloromethane
  5. washThe organic layer was washed sequentially with 0.1M aqueous citric acid, 0.1M aqueous NaH2PO4
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe sample was filtered
  8. customvolatiles removed
  9. customthe sample dried in vacuo

Sources & evidence

ORD record
ord-5eb9b274e45848b6866b9482e31390d9
Source dataset
uspto-grants-2012_03
Patent number
US08143243B2

Reaction notes

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