Ethanol → HCID 68797959, compound

HRID 505750Notes

Reaction equation

HRID 505750 reaction equation
F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[Cl:23][C:24]1[CH:25]=[C:26]([N:32]2[CH:40]([C:41]3[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=3)[CH:39]3[C:34]([C:35]4[CH:51]=[CH:50][C:49]([C:52]([OH:54])=O)=[CH:48][C:36]=4[CH2:37][CH2:38]3)=[N:33]2)[CH:27]=[CH:28][C:29]=1[C:30]#[N:31].C(O)C.C(N(CC)CC)C.[N:65]1([CH2:70][CH2:71][NH2:72])[CH2:69][CH2:68][CH2:67][CH2:66]1>CN(C)C=O>[Cl:23][C:24]1[CH:25]=[C:26]([N:32]2[CH:40]([C:41]3[CH:42]=[CH:43][C:44]([F:47])=[CH:45][CH:46]=3)[CH:39]3[C:34]([C:35]4[CH:51]=[CH:50][C:49]([C:52]([NH:72][CH2:71][CH2:70][N:65]5[CH2:69][CH2:68][CH2:67][CH2:66]5)=[O:54])=[CH:48][C:36]=4[CH2:37][CH2:38]3)=[N:33]2)[CH:27]=[CH:28][C:29]=1[C:30]#[N:31]

Participants

7

Reactant 5

HCID 702EthanolHCID 13441-PyrrolidineethanamineHCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 24983756HCID 24983756, compound

Product 1

HCID 68797959HCID 68797959, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (77 mg, 0.24 mmol) was added to a solution of (±)-(3RS,3aRS)-2-(3-chloro-4-cyanophenyl)-3-(4-fluorophenyl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid, Example 2 (89 mg, 0.20 mmol), triethylamine (0.056 mL, 0.40 mmol), and dimethylformamide (2.0 mL) at room temp. After 10 minutes, 2-(pyrrolidin-1-yl)ethanamine (0.051 mL, 0.40 mmol) was added. After 40 minutes, the reaction was quenched with 0.30 mL 3N hydrogen chloride and purified by reverse-phase HPLC (20 to 90% acetonitrile/water/0.05% trifluoroacetic acid). The purified fractions were combined, neutralized with saturated sodium bicarbonate solution, and concentrated until a precipitate formed. The precipitate was filtered, washed with water, and dried to give the title compound (yellow solid, 45.5 mg, 0.084 mmol, 42% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.80 (m, 1H), 1.64 (m, 4H), 1.79 (m, 1H), 2.46 (m, 4H), 2.54 (t, J=7.03 Hz, 2H), 2.91 (m, 2H), 3.35 (q, J=6.64 Hz, 2H), 3.95 (ddd, J=13.57, 11.03, 5.08 Hz, 1H), 5.92 (d, J=11.33 Hz, 1H), 7.15 (m, 6H), 7.65 (d, J=8.59 Hz, 1H), 7.69 (s, 1H), 7.75 (dd, J=8.20, 1.56 Hz, 1H), 8.10 (d, J=8.20 Hz, 1H), 8.47 (t, J=5.86 Hz, 1H). ES-MS m/z 542 (M+H).

Workup

  1. waitAfter 40 minutes
  2. customthe reaction was quenched with 0.30 mL 3N hydrogen chloride
  3. custompurified by reverse-phase HPLC (20 to 90% acetonitrile/water/0.05% trifluoroacetic acid)
  4. concentrationconcentrated until a precipitate
  5. customformed
  6. filtrationThe precipitate was filtered
  7. washwashed with water
  8. customdried

Sources & evidence

ORD record
ord-e90cfd385692440a9f383aefe8b7a415
Source dataset
uspto-grants-2010_08
Patent number
US07781428B2

Reaction notes

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