3,3,3-Trifluoropropanal → 3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-N-[(S)-6-(3,3,3-trifluoro-propylamino)-4,5,6,7-tetrahydro-benzothiazol-2-yl]-benzamide

HRID 1468180Notes

Reaction equation

HRID 1468180 reaction equation
[NH2:1][C@H:2]1[CH2:33][CH2:32][C:5]2[N:6]=[C:7]([NH:9][C:10](=[O:31])[C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][N:18]4[CH:22]=[C:21]([C:23]5[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][CH:24]=5)[CH:20]=[N:19]4)[CH:12]=3)[S:8][C:4]=2[CH2:3]1.[F:34][C:35]([F:40])([F:39])[CH2:36][CH:37]=O.[C:41]([BH3-])#[N:42].[Na+].CO.C(Cl)Cl>C(O)(=O)C>[F:34][C:35]([F:40])([F:39])[CH2:36][CH2:37][N:42]([CH2:41][CH2:36][C:35]([F:40])([F:39])[F:34])[C@H:2]1[CH2:33][CH2:32][C:5]2[N:6]=[C:7]([NH:9][C:10](=[O:31])[C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][N:18]4[CH:22]=[C:21]([C:23]5[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][CH:24]=5)[CH:20]=[N:19]4)[CH:12]=3)[S:8][C:4]=2[CH2:3]1.[C:29]([C:26]1[CH:25]=[CH:24][C:23]([C:21]2[CH:20]=[N:19][N:18]([CH2:17][C:13]3[CH:12]=[C:11]([CH:16]=[CH:15][CH:14]=3)[C:10]([NH:9][C:7]3[S:8][C:4]4[CH2:3][C@@H:2]([NH:1][CH2:37][CH2:36][C:35]([F:40])([F:39])[F:34])[CH2:33][CH2:32][C:5]=4[N:6]=3)=[O:31])[CH:22]=2)=[CH:28][CH:27]=1)#[N:30]

Participants

7

Reactant 4

HCID 680283,3,3-TrifluoropropanalHCID 5003444Sodium cyanoborohydrideHCID 21226129Dichloromethane methanolHCID 56966525N-((S)-6-amino-4,5,6,7-tetrahydro-benzothiazol-2-yl)-3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-benzamide

Product 2

HCID 56966386N-{(S)-6-[bis-(3,3,3-trifluoro-propyl)-amino]-4,5,6,7-tetrahydro-benzothiazol-2-yl}-3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-benzamideYield 4%HCID 569663873-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-N-[(S)-6-(3,3,3-trifluoro-propylamino)-4,5,6,7-tetrahydro-benzothiazol-2-yl]-benzamideYield 55%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Dissolve N—((S)-6-amino-4,5,6,7-tetrahydro-benzothiazol-2-yl)-3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-benzamide (0.22 g, 0.48 mmol) and 3,3,3-trifluoropropionaldehyde (0.22 g, 1.94 mmol) and sodium cyanoborohydride (0.12 g, 1.94 mmol) into 5 mL 20% MeOH/CH2Cl2. Add 250 microL of acetic acid and stir overnight at room temperature. Concentrate the mixture and add aq. Na2CO3. Extract 4 times with EtOAc, washed 2 times with aq. Na2CO3 and once with H2O. Dry the organic phase and concentrate to give a clear oil. Purify via SiO2 prep plate chromatography, eluting with 6% MeOH/CH2Cl2/0.5% NH4OH to afford 0.013 g, 4% yield of N-{(S)-6-[bis-(3,3,3-trifluoro-propyl)-amino]-4,5,6,7-tetrahydro-benzothiazol-2-yl}-3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-benzamide as an oil MS, electrospray 647.8 (M+H), rt 2.11 min. and 147.6 mg, 55% yield of 3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-N—[(S)-6-(3,3,3-trifluoro-propylamino)-4,5,6,7-tetrahydro-benzothiazol-2-yl]-benzamide as a foamy resin. MS, electrospray 551.69 (M+H), rt 1.58 min.

Workup

  1. concentrationConcentrate the mixture
  2. additionadd aq. Na2CO3
  3. extractionExtract 4 times with EtOAc
  4. washwashed 2 times with aq. Na2CO3
  5. customDry the organic phase
  6. concentrationconcentrate
  7. customto give a clear oil
  8. customPurify via SiO2 prep plate chromatography
  9. washeluting with 6% MeOH/CH2Cl2/0.5% NH4OH

Sources & evidence

ORD record
ord-381a4e3bb97b4e7cbe0f45a35dc97d83
Source dataset
uspto-grants-2015_04
Patent number
US09000154B2

Reaction notes

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