Triethylamine → HCID 59166077, compound

HRID 2188972Notes

Reaction equation

HRID 2188972 reaction equation
[F:1][C:2]1([F:33])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=5)[C:26](O)=[O:27])[C:20]([CH3:32])=[CH:19][CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.[CH3:34][S:35]([NH2:38])(=[O:37])=[O:36].C(N(CC)CC)C>ClCCl>[F:33][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=5)[C:26]([NH:38][S:35]([CH3:34])(=[O:37])=[O:36])=[O:27])[C:20]([CH3:32])=[CH:19][CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 72879MethanesulfonamideHCID 16678941Lumacaftor

Product 1

HCID 59166077HCID 59166077, compoundYield 30.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(6-(1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (200 mg, 0.442 mmol) and methanesulfonamide (46.4 mg, 0.488 mmol) were dissolved in dichloromethane (2 mL) containing triethylamine (0.247 mL, 1.76 mmol). O-(7-Azabenzotriazol-1-yl)-N,N,N′-tetramethyluronium hexafluorophosphate (HATU, 185 mg, 0.487 mmol) was added and the solution was allowed to stir for 16 hours. The crude product was purified on 12 g of silica gel utilizing a gradient of 0-100% ethyl acetate in hexanes to yield 3-(6-(1-(2,2-difluorobenzo[d][1,3]-dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)-N-(methylsulfonyl)-benzamide (71 mg, 30%) as a white solid. ESI-MS m/z calc. 529.1. found 529.9 (M+1)+ Retention time 1.83 minutes. 1H NMR (400 MHz, CD3CN) δ 9.57 (s, 1H), 8.01 (d, J=8.4 Hz, 1H), 7.91-7.87 (m, 1H), 7.75 (s, 1H), 7.68-7.66 (m, 2H), 7.58-7.53 (m, 1H), 7.36-7.32 (m, 2H), 7.21 (d, J=8.2 Hz, 1H), 3.30 (s, 3H), 2.25 (s, 3H), 1.63-1.58 (m, 2H), 1.20-1.16 (m, 2H).

Workup

  1. customThe crude product was purified on 12 g of silica gel utilizing a gradient of 0-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-6933a8fbc0644ae1b8b3e03e62a2396a
Source dataset
uspto-grants-2012_12
Patent number
US08324207B2

Reaction notes

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