Boron Trichloride → HCID 50944027, compound

HRID 1484937Notes

Reaction equation

HRID 1484937 reaction equation
B(Cl)(Cl)Cl.C([NH:9][S:10]([C:13]1[S:14][C:15]([C:18]2[N:23]=[C:22]([NH:24][C:25]3[CH:29]=[C:28]([CH:30]4[CH2:32][CH2:31]4)[NH:27][N:26]=3)[C:21](/[CH:33]=[CH:34]/[CH2:35][OH:36])=[CH:20][N:19]=2)=[CH:16][CH:17]=1)(=[O:12])=[O:11])(C)(C)C>C(Cl)Cl>[CH:30]1([C:28]2[NH:27][N:26]=[C:25]([NH:24][C:22]3[C:21](/[CH:33]=[CH:34]/[CH2:35][OH:36])=[CH:20][N:19]=[C:18]([C:15]4[S:14][C:13]([S:10]([NH2:9])(=[O:12])=[O:11])=[CH:17][CH:16]=4)[N:23]=3)[CH:29]=2)[CH2:32][CH2:31]1

Participants

4

Reactant 2

HCID 25135Boron TrichlorideHCID 58169370HCID 58169370, compound2×

Product 1

HCID 50944027HCID 50944027, compoundYield 11.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

BCl3 (1 M in CH2Cl2, 0.5 mL, 6.0 mmol, 20 eq) was added to a stirred solution of (E)-N-tert-butyl-5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(3-hydroxyprop-1-enyl)pyrimidin-2-yl)thiophene-2-sulfonamide (Compound 214) (40 mg, 0.08 mmol) in CH2Cl2 (10 mL) at room temperature under nitrogen. The reaction mixture was stirred for 30 min and then quenched with aq. NaHCO3 in ice bath. The reaction mixture was extracted with ethyl acetate and washed with water, brine, dried and evaporated. The crude product was crystallized with THF/isopropyl to afford (E)-5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(3-hydroxyprop-1-enyl)pyrimidin-2-yl)thiophene-2-sulfonamide (Compound 281) (4 mg, 11%). LC-MS (m/z)=419 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.73-0.77 (m, 2H), 0.95-1.00 (m, 2H), 1.90-1.96 (m, 1H), 4.16 (d, J=4.4 Hz, 2H), 6.37 (dt, J=15.6 Hz, 4.8 Hz, 1H), 6.45 (s, 1H), 6.88 (d, J=15.6 Hz, 1H), 7.57 (d, J=4.4 Hz, 1H), 7.76 (d, J=4.0 Hz, 1H), 7.78 (s, 2H), 8.43 (s, 1H), 9.27 (s, 1H).

Workup

  1. customquenched with aq. NaHCO3 in ice bath
  2. extractionThe reaction mixture was extracted with ethyl acetate
  3. washwashed with water, brine
  4. customdried
  5. customevaporated
  6. customThe crude product was crystallized with THF/isopropyl

Sources & evidence

ORD record
ord-f7b0f3ac2724440294a2eeae30434bbc
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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