Formaldehyde → 3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-N-{(S)-6-[methyl-(3,3,3-trifluoro-propyl)-amino]-4,5,6,7-tetrahydro-benzothiazol-2-yl}-benzamide

HRID 1468181Notes

Reaction equation

HRID 1468181 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:37]=[CH:38][CH:39]=3)[C:18]([NH:20][C:21]3[S:22][C:23]4[CH2:29][C@@H:28]([NH:30][CH2:31][CH2:32][C:33]([F:36])([F:35])[F:34])[CH2:27][CH2:26][C:24]=4[N:25]=3)=[O:19])[CH:13]=2)=[CH:5][CH:4]=1)#[N:2].C=O.[C:42]([BH3-])#N.[Na+]>CO.C(Cl)Cl>[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:37]=[CH:38][CH:39]=3)[C:18]([NH:20][C:21]3[S:22][C:23]4[CH2:29][C@@H:28]([N:30]([CH3:42])[CH2:31][CH2:32][C:33]([F:36])([F:35])[F:34])[CH2:27][CH2:26][C:24]=4[N:25]=3)=[O:19])[CH:13]=2)=[CH:5][CH:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 569663873-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-N-[(S)-6-(3,3,3-trifluoro-propylamino)-4,5,6,7-tetrahydro-benzothiazol-2-yl]-benzamide

Product 1

HCID 569665273-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-N-{(S)-6-[methyl-(3,3,3-trifluoro-propyl)-amino]-4,5,6,7-tetrahydro-benzothiazol-2-yl}-benzamideYield 83.7%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

Stir a solution 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 (0.063 g, 0.11 mmol) and formaldehyde solution (0.08 mL, 1.14 mmol, 37 wt % in H2O) and sodium cyanoborohydride (0.014 g, 0.23 mmol) in 1 mL 20% MeOH/CH2Cl2 overnight at room temperature in a capped flask. Concentrate the mixture, add aq. H2O and extract the product 4×EtOAc, washed 3×H2O. Dry the mixture with a drying agent and concentrate. Purify the product on a prep plate eluting with 5% MeOH/CH2Cl2 which affords 0.052 g, 80% yield of 3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-N-{(S)-6-[methyl-(3,3,3-trifluoro-propyl)-amino]-4,5,6,7-tetrahydro-benzothiazol-2-yl}-benzamide as a clear resin. MS, electrospray 565.71 (M+H), room temperature 1.60 min. The following compound is prepared analogously (Example 11)

Workup

  1. concentrationConcentrate the mixture
  2. additionadd aq. H2O
  3. extractionextract the product 4×EtOAc
  4. washwashed 3×H2O
  5. customDry the mixture with a drying agent
  6. concentrationconcentrate
  7. customPurify the product on a prep plate
  8. washeluting with 5% MeOH/CH2Cl2 which

Sources & evidence

ORD record
ord-f1505285c9eb4be08646bc3b4cbf65bc
Source dataset
uspto-grants-2015_04
Patent number
US09000154B2

Reaction notes

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