Acetic Acid → HCID 46213239, compound

HRID 2363526Notes

Reaction equation

HRID 2363526 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[C:5]([CH:16]=[CH:17][CH:18]=1)[CH2:6][N:7]1[CH2:11][C@H:10]2[C@@H:12]([NH2:15])[CH2:13][CH2:14][C@H:9]2[CH2:8]1.C(O[C:24]1(O[Si](C)(C)C)[CH2:26][CH2:25]1)C.[C:32](O)(=O)[CH3:33].[C:36]([BH3-])#N>ClCCl>[CH:33]1([N:15]([CH:24]2[CH2:25][CH2:26]2)[C@@H:12]2[C@H:10]3[C@H:9]([CH2:8][N:7]([CH2:6][C:5]4[CH:16]=[CH:17][CH:18]=[C:3]([C:2]([F:19])([F:1])[F:20])[CH:4]=4)[CH2:11]3)[CH2:14][CH2:13]2)[CH2:32][CH2:36]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 498716Cyano-borohydrideHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 66590379(3aS*,4S*,6aR*)-2-(3-(trifluoromethyl)benzyl)octahydrocyclopenta[c]pyrrol-4-amine

Product 1

HCID 46213239HCID 46213239, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(3aS*,4S*,6aR*)-2-(3-(Trifluoromethyl)benzyl)octahydrocyclopenta[c]pyrrol-4-amine (228 mg, 0.802 mmol) from Example 122 Step E and (1-ethoxycyclopropoxy)trimethylsilane (140 mg, 0.802 mmol) were combined in dichloromethane (1.5 mL) and 5 mL of acetic acid was added. The reaction was stirred at room temperature for 20 minutes, and then PS-cyanoborohydride (343 mg, 0.802 mmol) was added. The reaction was heated to 40° C. overnight. Silica gel chromatography eluting with 1-10% methanol (2 N ammonia)/dichloromethane to gave the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 7.58 (s, 1H), 7.48 (d, J=7.6, 2H), 7.42 (d, J=7.6, 1H), 3.64 (d, J=13.6, 1H), 3.51 (d, J=13.6, 1H), 2.94-2.82 (m, 3H), 2.80-2.71 (m, 2H), 2.55 (dd, J=5.4, 9.4, 3H), 2.41 (t, J=8.3, 1H), 2.16 (dd, J=4.7, 8.7, 1H), 1.97-1.70 (m, 7H), 1.70-1.59 (m, 3H), 1.40 (dd, J=6.7, 12.6, 1H); MS (ESI+) m/z 365 (M+H)+.

Workup

  1. temperatureThe reaction was heated to 40° C. overnight
  2. washSilica gel chromatography eluting with 1-10% methanol (2 N ammonia)/dichloromethane

Sources & evidence

ORD record
ord-a438595a0c0a4f2e8b1e3bb09b75c224
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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