Acetic Acid → HCID 66996874, compound

HRID 2363628Notes

Reaction equation

HRID 2363628 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH:11]=O)=[CH:5]2.[F:13][C:14]([F:31])([F:30])[C:15]1[CH:16]=[CH:17][C:18]([N:21]2[CH2:25][C@@H:24]3[C@@H:26]([NH2:29])[CH2:27][CH2:28][C@@H:23]3[CH2:22]2)=[N:19][CH:20]=1.C(O)(=O)C.C([BH3-])#N>ClCCl>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH2:11][NH:29][C@@H:26]1[C@@H:24]3[C@@H:23]([CH2:22][N:21]([C:18]4[CH:17]=[CH:16][C:15]([C:14]([F:31])([F:30])[F:13])=[CH:20][N:19]=4)[CH2:25]3)[CH2:28][CH2:27]1)=[CH:5]2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 498716Cyano-borohydrideHCID 189681295-Fluoro-1H-indole-2-carbaldehydeHCID 66590965(3aR,4S,6aS)-2-(5-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-amine

Product 1

HCID 66996874HCID 66996874, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared by combining 5-fluoro-1H-indole-2-carbaldehyde (30.1 mg, 0.184 mmol) and (3aR,4S,6aS)-2-(5-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-amine (50 mg, 0.184 mmol) from Example 262 Step B in dichloromethane (0.2 mL) to give a colorless solution. 0.2 mL of acetic acid was added. The reaction was stirred at ambient temperature for 30 minutes, then PS-cyanoborohydride (166 mg, 0.369 mmol) was added. After 18 hours, the reaction was filtered and the solvent was removed in vacuo. The crude material was purified using a 12 g silica gel cartridge eluted with 1-10% methanol (2 N ammonia)/dichloromethane to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 12.14 (s, 1H), 8.64 (dd, J=1.5, 0.7, 1H), 7.69 (dd, J=8.9, 2.5, 1H), 7.54-7.46 (m, 2H), 7.14-7.07 (m, 1H), 6.61 (d, J=1.2, 1H), 6.36 (d, J=8.9, 1H), 4.12-4.00 (m, 2H), 3.56 (ddd, J=21.0, 9.4, 3.4, 2H), 3.48-3.40 (m, 1H), 3.28 (ddd, J=3.7, 2.1, 0.9, 1H), 3.04 (dd, J=11.0, 5.8, 1H), 2.78-2.68 (m, 1H), 2.57-2.50 (m, 1H), 2.31-2.04 (m, 1H), 2.02-1.91 (m, 2H), 1.55-1.44 (m, 1H), 1.38-1.28 (m, 1H); MS (ESI+) m/z 419 (M+H)+.

Workup

  1. customThe title compound was prepared
  2. customto give a colorless solution
  3. waitAfter 18 hours
  4. filtrationthe reaction was filtered
  5. customthe solvent was removed in vacuo
  6. customThe crude material was purified
  7. washeluted with 1-10% methanol (2 N ammonia)/dichloromethane

Sources & evidence

ORD record
ord-d04029f5a2384e0e8ff7199bccf206c8
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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