(3S)-pyrrolidin-3-ol → (S)-1-[(S)-1-(4-Fluorophenyl)-6-[6-morpholin-4-yl-pyridine-3-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-ylmethyl]-pyrrolidin-3-ol

HRID 1907327Notes

Reaction equation

HRID 1907327 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([CH:21]=O)([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][N:17]([S:23]([C:26]2[CH:27]=[N:28][C:29]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[CH:30][CH:31]=2)(=[O:25])=[O:24])[CH2:16][CH2:15]4)=[CH:4][CH:3]=1.[NH:38]1[CH2:42][CH2:41][C@H:40]([OH:43])[CH2:39]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([CH2:21][N:38]5[CH2:42][CH2:41][C@H:40]([OH:43])[CH2:39]5)([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][N:17]([S:23]([C:26]2[CH:27]=[N:28][C:29]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[CH:30][CH:31]=2)(=[O:24])=[O:25])[CH2:16][CH2:15]4)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 2733874(3S)-pyrrolidin-3-olHCID 5049666Sodium triacetoxyborohydrideHCID 86669996HCID 86669996, compound

Product 1

HCID 56848492(S)-1-[(S)-1-(4-Fluorophenyl)-6-[6-morpholin-4-yl-pyridine-3-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-ylmethyl]-pyrrolidin-3-olYield 29.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

A solution of (R)-1-(4-fluorophenyl)-6-[6-morpholin-4-yl-pyridine-3-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carbaldehyde (0.074 g) in dry dichloroethane (2.8 mL) was treated with (S)-pyrrolidin-3-ol (0.062 g) and 4A powdered molecular sieves (0.14 g) for 4 hours. Sodium triacetoxyborohydride (0.045 g) was added and the reaction mixture stirred for 20 hours. The reaction mixture was diluted with dichloromethane, washed with saturated aqueous sodium hydrogen carbonate solution and brine. The organic extracts were dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by preparative reverse-phase HPLC eluting with a mixture of acetonitrile and water containing 0.1% formic acid (1:19 to 7:3 by volume) to give the title compound as a white solid (0.025 g). 1H NMR (400 MHz, CHCl3-d): δ 8.54 (d, 1H), 8.24 (s, 1H), 7.81 (dd, 1H), 7.43-7.32 (m, 3H), 7.16 (t, 2H), 6.63 (d, 1H), 6.28 (d, 1H), 4.40 (s, 1H), 4.30 (d, 1H), 3.90 (d, 1H), 3.81 (t, 4H), 3.67 (t, 4H), 3.36-3.23 (m, 2H), 3.13-3.01 (m, 3H), 2.78-2.63 (m, 2H), 2.54 (d, 1H), 2.44-2.25 (m, 3H), 2.24-2.13 (m, 2H), 1.90 (dt, 1H).

Workup

  1. washwashed with saturated aqueous sodium hydrogen carbonate solution and brine
  2. dry with materialThe organic extracts were dried over sodium sulphate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by preparative reverse-phase HPLC
  5. washeluting with a mixture of acetonitrile and water containing 0.1% formic acid (1:19 to 7:3 by volume)

Sources & evidence

ORD record
ord-8c8a2632a0ba4a1b932f16dd4a445614
Source dataset
uspto-grants-2013_12
Patent number
US08598154B2

Reaction notes

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