NADPH → (2R)-2-(4-((2R)-2-((4,4-difluoro-1-piperidinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

HRID 1972412Notes

Reaction equation

[F:1][C:2]1([F:36])[CH2:7][CH2:6][N:5]([CH2:8][C@H:9]2[CH2:14][N:13]([S:15]([C:18]3[S:19][CH:20]=[CH:21][CH:22]=3)(=[O:17])=[O:16])[CH2:12][CH2:11][N:10]2[C:23]2[CH:28]=[CH:27][C:26]([C@:29]([OH:35])([CH3:34])[C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=2)[CH2:4][CH2:3]1.FC1(F)CCN(C[C@@H]2CN(S(C3SC=CC=3)(=O)=O)CCN2C2C=CC([C@@](O)(C)C(F)(F)F)=CC=2)CC1.FC1(F)CCN(C[C@H]2CN(S(C3SC=CC=3)(=O)=O)CCN2C2C=CC([C@@](O)(C)C(F)(F)F)=CC=2)CC1.C1N=C(N)C2N=CN([C@@H]3O[C@H](COP(OP(OC[C@H]4O[C@@H](N5C=C(C(N)=O)CC=C5)[C@H](O)[C@@H]4O)(O)=O)(O)=O)[C@@H](O)[C@H]3OP(O)(O)=O)C=2N=1>>[F:36][C:2]1([F:1])[CH2:3][CH2:4][N:5]([CH2:8][C@@H:9]2[CH2:14][N:13]([S:15]([C:18]3[S:19][CH:20]=[CH:21][CH:22]=3)(=[O:16])=[O:17])[CH2:12][CH2:11][N:10]2[C:23]2[CH:28]=[CH:27][C:26]([C@:29]([OH:35])([CH3:34])[C:30]([F:31])([F:33])[F:32])=[CH:25][CH:24]=2)[CH2:6][CH2:7]1

Participants

Reactant 4

HCID 5884NADPH

HCID 66582461(2R)-2-(4-((2S)-2-((4,4-difluoro-1-piperidinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

HCID 66582744(2S)-2-(4-((2S)-2-((4,4-difluoro-1-piperidinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

HCID 66582745(2S)-2-(4-((2R)-2-((4,4-difluoro-1-piperidinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

Product 1

HCID 70655831(2R)-2-(4-((2R)-2-((4,4-difluoro-1-piperidinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

Procedure

(2R)-2-(4-((2S)-2-((4,4-difluoro-1-piperidinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol; (2S)-2-(4-((2R)-2-((4,4-difluoro-1-piperidinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol; (2S)-2-(4-((2S)-2-((4,4-difluoro-1-piperidinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol. 1H NMR (400 MHz, DMSO-d6) δ 8.08-8.06 (dd, J=5.1, 1.1 Hz, 1H), 7.70-7.68 (dd, J=3.7, 1.1 Hz, 1H), 7.38-7.34 (d, J=9.2 Hz, 2H), 7.32-7.30 (m, 1H), 6.89-6.87 (d, J=9.2 Hz, 2H), 4.15-4.11 (m, 1H), 3.46-3.38 (m, 3H), 3.15-3.08 (m, 1H), 2.69-2.63 (m, 1H), 2.59-2.52 (m, 2H), 2.46-2.38 (m, 4H), 2.30-2.25 (m, 1H), 1.79-1.73 (m, 4H), 1.61 (s, 3H). m/z (ESI, +ve ion) 554.2 (M+H)+. GK-GKRP EC50 (NADPH-coupled)=1.05 μM; GK-GKRP EC50 (LC MS/MS)=1.53 μM.

Sources & evidence

ORD record: ord-758b792787914f3e920ace7af24f86ca
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431563B2

Reaction notes

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