Methanol → (R)-1-[5-(4-tert-Butyl-cyclohexyloxy)-benzothiazol-2-ylmethyl]-pyrrolidine-3-carboxylic acid

HRID 713971Notes

Reaction equation

HRID 713971 reaction equation
[NH:1]1[CH2:5][CH2:4][C@@H:3]([C:6]([OH:8])=[O:7])[CH2:2]1.C(N(CC)C(C)C)(C)C.CO.[C:20]([CH:24]1[CH2:29][CH2:28][CH:27]([O:30][C:31]2[CH:32]=[CH:33][C:34]3[S:38][C:37]([CH:39]=O)=[N:36][C:35]=3[CH:41]=2)[CH2:26][CH2:25]1)([CH3:23])([CH3:22])[CH3:21].C([BH3-])#N.[Na+]>>[C:20]([CH:24]1[CH2:29][CH2:28][CH:27]([O:30][C:31]2[CH:32]=[CH:33][C:34]3[S:38][C:37]([CH2:39][N:1]4[CH2:5][CH2:4][C@@H:3]([C:6]([OH:8])=[O:7])[CH2:2]4)=[N:36][C:35]=3[CH:41]=2)[CH2:26][CH2:25]1)([CH3:23])([CH3:22])[CH3:21]

Participants

6

Reactant 5

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 1501970(3R)-3-Pyrrolidinecarboxylic acidHCID 5003444Sodium cyanoborohydrideHCID 866684285-(4-tert-Butyl-cyclohexyloxy)-benzothiazole-2-carbaldehyde

Product 1

HCID 66926788(R)-1-[5-(4-tert-Butyl-cyclohexyloxy)-benzothiazol-2-ylmethyl]-pyrrolidine-3-carboxylic acid

Conditions

Temperature
0 °C

Procedure

(R)-Pyrrolidine-3-carboxylic acid (100 mg, 0.9 mmol) (HCl salt) was combined with N,N-Diisopropylethylamine (300 uL, 2 mmol) in Methanol (4.0 mL, 98 mmol) and stirred for 15 min. 5-(4-tert-Butyl-cyclohexyloxy)-benzothiazole-2-carbaldehyde (10.0E2 mg, 0.33 mmol) was then added and the mixture was stirred at RT for 30 minutes. After 30 minutes the reaction was cooled to 0° C. and Sodium cyanoborohydride (100 mg, 2 mmol) was added in two portions. The reaction was then allowed to warm to RT while stirring overnight. The reaction was then purified directly on the Gilson (10-90% CH3CN/H2O (0.1% TFA), 19×150 cm C18, RT=8.6 min) The product was then dried on the highvac to give the title compound as a white solid. 1H NMR (400 MHz, MeOD) Shift=8.00-7.78 (m, 1H), 7.69-7.51 (m, 1H), 7.27-7.05 (m, 1H), 5.09-4.93 (m, 3H), 4.39-4.21 (m, 1H), 4.01-3.39 (m, 4H), 2.65-2.18 (m, 3H), 2.01-1.80 (m, 2H), 1.53-1.04 (m, 6H), 0.92 (s, 9H). MS (ESI, M+1): 417.30.

Workup

  1. stirringthe mixture was stirred at RT for 30 minutes
  2. temperatureto warm to RT
  3. stirringwhile stirring overnight
  4. customThe reaction was then purified directly on the Gilson (10-90% CH3CN/H2O (0.1% TFA), 19×150 cm C18, RT=8.6 min) The product
  5. customwas then dried on the highvac

Sources & evidence

ORD record
ord-fa6f11a00a33478eb181dd103f6c1fc9
Source dataset
uspto-grants-2015_11
Patent number
US09186367B2

Reaction notes

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