Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → HCID 86697424, compound

HRID 1478254Notes

Reaction equation

HRID 1478254 reaction equation
N1(C2CCCCCCCCCC2)CCCN=CCCCCC1.[S:23]1[CH:27]=[CH:26][CH:25]=[C:24]1[C:28]1[CH:29]=[N:30][N:31]2[CH:36]=[CH:35][C:34](=O)[NH:33][C:32]=12.[C:38]([O:42][C:43](=[O:49])[N:44]([CH2:46][CH2:47][NH2:48])[CH3:45])([CH3:41])([CH3:40])[CH3:39].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(#N)C>[C:38]([O:42][C:43](=[O:49])[N:44]([CH3:45])[CH2:46][CH2:47][NH:48][C:34]1[CH:35]=[CH:36][N:31]2[N:30]=[CH:29][C:28]([C:24]3[S:23][CH:27]=[CH:26][CH:25]=3)=[C:32]2[N:33]=1)([CH3:41])([CH3:40])[CH3:39]

Participants

6

Reactant 4

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 2756424N-Boc-N-methylethylenediamineHCID 1296629601,8-Diazabicycloundec-7ene2×HCID 136378628HCID 136378628, compound

Product 1

HCID 86697424HCID 86697424, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,8-Diazabicycloundec-7-ene (DBU) [6674-22-2] (0.4 mL, 2.5 mmol) was added to an ambient temperature, stirred, turbid solution of 3-thiophen-2-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one (354.3 mg, 1.6 mmol), (2-amino-ethyl)-methyl-carbamic acid tert-butyl ester [121492-06-6] (852.2 mg, 4.9 mmol), and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) [56602-33-6] (937.7 mg, 2.1 mmol) in acetonitrile (16 mL). Upon addition of the DBU the turbidity clears and the solution was permitted to stir for 2 d then partitioned between brine and ethyl acetate. The extract was dried (MgSO4) and flash chromatographed (silica gel, eluted with 10% (v/v) methanol/ethyl acetate). Evaporation of product fractions yielded an oil which was crystallized from heptane to provide methyl-[2-(3-thiophen-2-yl-pyrazolo[1,5-a]pyrimidin-5-ylamino)-ethyl]-carbamic acid tert-butyl ester as 333.6 mg of yellow, fine crystalline powder, mp. 140-141° C. 1H NMR (400 MHz, DMSO-d6) δ ppm (rotomers present) 1.16-1.28 (m, 5 H) 1.37 (br. s., 3 H) 2.51 (s, 1 H) 2.85 (br. s., 3 H) 3.47 (br. s., 1 H) 3.55 (br. s., 3 H) 6.28 (d, J=6.82 Hz, 1 H) 7.04 (dd, J=5.05, 3.54 Hz, 1 H) 7.30 (dd, J=5.05, 1.01 Hz, 1 H) 7.41 (br. s., 1 H) 7.80 (br. s., 1 H) 8.19 (s, 1 H) 8.48 (d, J=7.07 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ ppm 27.81, 27.96, 33.75, 38.41, 46.32, 78.13, 100.28, 100.76, 120.16, 121.75, 126.90, 135.01, 135.20, 140.78, 143.74, 154.91, 155.81. LRMS (ESI) m/z 374.1 [(M+H)]+, calc'd for C18H23N5O2S: 373.48.

Workup

  1. stirringto stir for 2 d
  2. customthen partitioned between brine and ethyl acetate
  3. dry with materialThe extract was dried (MgSO4) and flash
  4. customchromatographed
  5. wash(silica gel, eluted with 10% (v/v) methanol/ethyl acetate)
  6. customEvaporation of product fractions
  7. customyielded an oil which
  8. customwas crystallized from heptane

Sources & evidence

ORD record
ord-f98e0c8de6374a46bad77723a006706f
Source dataset
uspto-grants-2016_08
Patent number
US09403832B2

Reaction notes

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