Water → HCID 178516970, compound

HRID 707323Notes

Reaction equation

HRID 707323 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([NH:15][C:16]2[C:21]([NH:22][CH:23]3[CH2:25][CH2:24]3)=[CH:20][C:19]([F:26])=[CH:18][N:17]=2)[CH2:12]1.C(N(CC)C(C)C)(C)C.Cl[C:37](Cl)([O:39]C(=O)OC(Cl)(Cl)Cl)Cl.O>ClCCl>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([N:15]2[C:16]3=[N:17][CH:18]=[C:19]([F:26])[CH:20]=[C:21]3[N:22]([CH:23]3[CH2:24][CH2:25]3)[C:37]2=[O:39])[CH2:12]1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 178506000HCID 178506000, compound

Product 1

HCID 178516970HCID 178516970, compoundYield 31.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N2-(Trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-N3-cyclopropyl-5-fluoropyridine-2,3-diamine (0.051 g, 0.138 mmol) was dissolved in a mixture of dichloromethane (10 mL) and N,N-diisopropylethylamine (0.100 ml, 0.575 mmol) and cooled in an ice bath under nitrogen. Triphosgene (0.041 g, 0.138 mmol) was added in one portion. The reaction allowed to stir in the ice bath and warm to room temperature over 14 hours. Water (5 mL) and dichloromethane (10 mL) were added and the reaction stirred vigorously. The phases were separated and the organic dried with magnesium sulfate before evaporating to dryness under reduced pressure. Purification using silica chromatography (first column 0-10% methanol in dichloromethane gradient, repurify using hexane to ethyl acetate gradient) gave 3-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-1-cyclopropyl-6-fluoro-1H-imidazo[4,5-b]pyridin-2(3H)-one (0.017 g, 0.043 mmol, 31.1% yield). M+1: 396. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.97-1.04 (m, 2 H) 1.10-1.17 (m, 2 H) 2.47-2.58 (m, 2 H) 2.88 (tt, J=6.92, 3.55 Hz, 1 H) 3.45-3.58 (m, 2 H) 4.55-4.65 (m, 1 H) 5.33 (quin, J=8.46 Hz, 1 H) 6.16 (br. s., 1 H) 7.05-7.12 (m, 1 H) 7.17 (dd, J=8.22, 2.35 Hz, 1 H) 7.25-7.35 (m, 1 H) 7.57 (d, J=8.02 Hz, 1 H) 7.60 (d, J=7.82 Hz, 1 H) 7.93 (t, J=2.15 Hz, 1 H).

Workup

  1. temperaturecooled in an ice bath under nitrogen
  2. customThe phases were separated
  3. dry with materialthe organic dried with magnesium sulfate
  4. custombefore evaporating to dryness under reduced pressure
  5. customPurification
  6. customsilica chromatography (first column 0-10% methanol in dichloromethane gradient, repurify using hexane to ethyl acetate gradient)

Sources & evidence

ORD record
ord-340f9b5d35ca4a8eb54e94324863873b
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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