Diisopropylethylamine → ((S)-2-{3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-benzoylamino}-4,5,6,7-tetrahydro-benzothiazol-6-yl)-carbamic acid tert-butyl ester

HRID 1468178Notes

Reaction equation

HRID 1468178 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[N:11][N:12]([CH2:14][C:15]3[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=3)[C:18]([OH:20])=O)[CH:13]=2)=[CH:5][CH:4]=1)#[N:2].[C:24]([O:28][C:29](=[O:41])[NH:30][C@H:31]1[CH2:40][CH2:39][C:34]2[N:35]=[C:36]([NH2:38])[S:37][C:33]=2[CH2:32]1)([CH3:27])([CH3:26])[CH3:25].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C>O.CN(C=O)C>[C:24]([O:28][C:29](=[O:41])[NH:30][C@H:31]1[CH2:40][CH2:39][C:34]2[N:35]=[C:36]([NH:38][C:18](=[O:20])[C:17]3[CH:21]=[CH:22][CH:23]=[C:15]([CH2:14][N:12]4[CH:13]=[C:9]([C:6]5[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=5)[CH:10]=[N:11]4)[CH:16]=3)[S:37][C:33]=2[CH2:32]1)([CH3:27])([CH3:25])[CH3:26]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 49844272tert-butyl N-[(6S)-2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl]carbamateHCID 675082023-[4-(4-Cyano-phenyl)-pyrazol-1-ylmethyl]-benzoic acid

Product 1

HCID 56966818((S)-2-{3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-benzoylamino}-4,5,6,7-tetrahydro-benzothiazol-6-yl)-carbamic acid tert-butyl esterYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Dissolve 3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-benzoic acid (0.25 g, 0.82 mmol) and ((S)-2-amino-4,5,6,7-tetrahydro-benzothiazol-6-yl)-carbamic acid tert-butyl ester (0.22 g, 0.82 mmol) and TBTU (0.40 g, 1.24 mmol) and N,N-diisopropylethylamine (0.40 ml, 2.47 mmol) into 1.5 mL dry DMF and stir overnight at room temperature under Ar. Pour the reaction into H2O, giving a precipitate. Filter the solid, wash with H2O, and dry. Extract the filtrate 3 times with EtOAc and washed 4 times with H2O, 3 times with aq. NH4Cl and once with aq.Na2CO3. Dry the organic phase and concentrate to give an oil. Both crops are combined and purified via prep plate chromatography eluting with 3% MeOH/CH2Cl2 to give 0.42 g, 92% yield as a clear hard resin of ((S)-2-{3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-benzoylamino}-4,5,6,7-tetrahydro-benzothiazol-6-yl)-carbamic acid tert-butyl ester.

Workup

  1. additionPour
  2. customgiving a precipitate
  3. filtrationFilter the solid
  4. washwash with H2O
  5. customdry
  6. extractionExtract the filtrate 3 times with EtOAc
  7. washwashed 4 times with H2O, 3 times with aq. NH4Cl
  8. customDry the organic phase
  9. concentrationconcentrate
  10. customto give an oil
  11. custompurified via prep plate chromatography
  12. washeluting with 3% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-288e10fb2bab44c1bd81c645699a339e
Source dataset
uspto-grants-2015_04
Patent number
US09000154B2

Reaction notes

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