HCID 131730632, compound → HCID 67344959, compound

HRID 1257666Notes

Reaction equation

HRID 1257666 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:27]([O-:29])=[O:28])[C:18]([NH:19][C@H:20]4[CH2:25][CH2:24][CH2:23][C@H:22]([OH:26])[CH2:21]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(S(N2C3=NC=C([N+]([O-])=O)C(N[C@@H]4CCC[C@H](O)C4)=C3C=C2)(=O)=O)C=CC=CC=1>>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:27]([O-:29])=[O:28])[C:18]([NH:19][CH:20]4[CH2:25][CH2:24][CH2:23][CH:22]([OH:26])[CH2:21]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

3

Reactant 2

HCID 131730632HCID 131730632, compoundHCID 131730633HCID 131730633, compound

Product 1

HCID 67344959HCID 67344959, compound

Procedure

A stirred suspension of 1-Benzenesulfonyl-4-chloro-5-nitro-1H-pyrrolo[2,3-b]pyridine (40.00 g, 118.4 mmol) and 3-amino-cyclohexanol (13.99 g, 121.5 mmol, mixture of four stereoisomers) in isopropyl alcohol (150 ml) was treated with N,N-diisopropylethylamine (30.94 ml, 117.65 mmol) and heated at about 82° C. overnight. The reaction mixture was concentrated under reduced pressure to give the crude product, which was purified in four batches by ISCO column chromatography (0-100% Ethyl acetate in heptane), to afford 8.84 g of the trans racemic product as a yellow solid (16.2% yield), and 27.97 g of the cis racemic product as a yellow solid (52.5% yield). In addition 8.66 g of a mixture of cis and trans racemic products (42% trans, 58% cis) was obtained as a yellow solid. Trans (racemic) 3-(1-Benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclohexanol. LCMS (Method M, ESI): RT=2.61 min, m+H=417.2; 1H NMR (400 MHz, DMSO) δ 8.88 (d, J=11.4 Hz, 1H), 8.12 (d, J=8.0 Hz, 1H), 7.83 (d, J=4.1 Hz, 1H), 7.76 (t, J=7.3 Hz, 1H), 7.65 (t, J=7.7 Hz, 1H), 7.18 (d, J=4.2 Hz, 1H), 4.77 (d, J=3.5 Hz, 1H), 4.36 (s, 1H), 3.99 (d, J=8.4 Hz, 1H), 1.99 (s, 1H), 1.90 (s, 1H), 1.77 (s, 1H), 1.66 (t, J=10.8 Hz, 1H), 1.59-1.46 (m, 2H), 1.25 (s, 1H), 0.85 (d, J=7.0 Hz, 1H). Cis (racemic) 3-(1-Benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclohexanol. LCMS (Method M): RT=2.47 min, m+H=417.3; 1H NMR (400 MHz, DMSO) δ 8.89 (s, 1H), 8.12 (d, J=7.8 Hz, 2H), 7.85-7.72 (m, 2H), 7.65 (t, J=7.8 Hz, 2H), 6.99 (d, J=4.2 Hz, 1H), 4.89 (d, J=3.8 Hz, 1H), 4.26-4.14 (m, 1H), 3.77 (d, J=3.6 Hz, 1H), 2.05 (d, J=12.4 Hz, 1H), 1.84 (s, 1H), 1.74 (d, J=13.0 Hz, 2H), 1.60-1.28 (m, 5H).

Workup

  1. customwas obtained as a yellow solid

Sources & evidence

ORD record
ord-a03c65c0ed0f40fcbba6a7eb6d1b17b9
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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