Dichloromethane → HCID 86722385, compound

HRID 718787Notes

Reaction equation

HRID 718787 reaction equation
F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+:12]1[C:20]2[C:15](=NC=C[CH:19]=2)[N+]([O-])=N1)C.[F:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[C:40]3[CH:39]=[C:38]4[CH2:41][CH2:42][CH2:43][CH:44]5[CH2:49][C:48]([O:54][Si:55]([CH2:60][CH3:61])([CH2:58][CH3:59])[CH2:56][CH3:57])([C:50]([F:53])([F:52])[F:51])[CH2:47][CH2:46][C:45]5([C:62]([OH:64])=O)[C:37]4=[CH:36][C:35]=3[CH:34]=[N:33]2)=[CH:28][CH:27]=1.C1(N)CC1.C(Cl)Cl>CN(C=O)C>[CH:20]1([NH:12][C:62]([C:45]23[CH2:46][CH2:47][C:48]([O:54][Si:55]([CH2:60][CH3:61])([CH2:56][CH3:57])[CH2:58][CH3:59])([C:50]([F:52])([F:51])[F:53])[CH2:49][CH:44]2[CH2:43][CH2:42][CH2:41][C:38]2[C:37]3=[CH:36][C:35]3[CH:34]=[N:33][N:32]([C:29]4[CH:28]=[CH:27][C:26]([F:25])=[CH:31][CH:30]=4)[C:40]=3[CH:39]=2)=[O:64])[CH2:15][CH2:19]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 69828CyclopropylamineHCID 86722383HCID 86722383, compoundHCID 178484293HCID 178484293, compound2×

Product 1

HCID 86722385HCID 86722385, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (0.201 g, 0.530 mmol) was added to a solution of rac-(3R,4aR,12bS)-9-(4-fluorophenyl)-3-((triethylsilyl)oxy)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carb oxylic acid (43, R1=4-Fluorophenyl, R3=Trifluoromethyl) (0.235 g, 0.407 mmol), cyclopropanamine (0.093 g, 1.6 mmol), N-ethyl-N,N-diisopropylethylamine (0.285 mL, 1.63 mmol), DCM (5 mL), and DMF (1 mL). After about 24 h, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (0.020 g, 0.053 mmol) was added. After about 24 h, the reaction mixture was partitioned between DCM (50 mL) and sat. aq. NaHCO3 (10 mL). The organic layer was washed with water (10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel (40 g) using a gradient of 0-17% EtOAc in heptane. The product fractions were combined and concentrated under reduced pressure to give rac-(3R,4aR,12bS)—N-cyclopropyl-9-(4-fluorophenyl)-3-((triethylsilyl)oxy)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carboxamide (44, R1=4-Fluorophenyl, R2′=Cyclopropyl, R3=Trifluoromethyl) (0.230 g. 92% yield); LC/MS, method 4, Rt=2.65 min.; MS m/z: 616 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J=0.9 Hz 1H), 7.86 (s, 1H), 7.73-7.65 (m, 2H), 7.45 (s, 1H), 7.29-7.22 (m, 2H), 4.99 (s, 1H), 2.93-2.72 (m, 2H), 2.72-2.46 (m, 4H), 2.26-2.08 (m, 2H), 2.08-1.87 (m, 3H), 1.75-1.63 (m, 2H), 1.42-1.29 (m, 1H), 1.05-0.96 (m, 9H), 0.78-0.60 (m, 8H), 0.32-0.15 (m, 2H).

Workup

  1. waitAfter about 24 h
  2. customthe reaction mixture was partitioned between DCM (50 mL) and sat. aq. NaHCO3 (10 mL)
  3. washThe organic layer was washed with water (10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified on silica gel (40 g)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b9fdf23308054165a9f3e8323eb23add
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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